Effect of estrogen on tendon collagen synthesis, tendon structural characteristics, and biomechanical properties in postmenopausal women

The knowledge about the effect of estradiol on tendon connective tissue is limited. Therefore, we studied the influence of estradiol on tendon synthesis, structure, and biomechanical properties in postmenopausal women. Nonusers (control, n = 10) or habitual users of oral estradiol replacement therapy (ERT, n = 10) were studied at rest and in response to one-legged resistance exercise. Synthesis of tendon collagen was determined by stable isotope incorporation [fractional synthesis rate (FSR)] and microdialysis technique (NH(2)-terminal propeptide of type I collagen synthesis). Tendon area and fibril characteristics were determined by MRI and transmission electron microscopy, whereas tendon biomechanical properties were measured during isometric maximal voluntary contraction by ultrasound recording. Tendon FSR was markedly higher in ERT users (P < 0.001), whereas no group difference was seen in tendon NH(2)-terminal propeptide of type I collagen synthesis (P = 0.32). In ERT users, positive correlations between serum estradiol (s-estradiol) and tendon synthesis were observed, whereas change in tendon synthesis from rest to exercise was negatively correlated to s-estradiol. Tendon area, fibril density, fibril volume fraction, and fibril mean area did not differ between groups. However, the percentage of medium-sized fibrils was higher in ERT users (P < 0.05), whereas the percentage of large fibrils tended to be greater in control (P = 0.10). A lower Young's modulus (GPa/%) was found in ERT users (P < 0.05). In conclusion, estradiol administration was associated with higher tendon FSR and a higher relative number of smaller fibrils. Whereas this indicates stimulated collagen turnover in the resting state, collagen responses to exercise were negatively associated with s-estradiol. These results indicate a pivotal role for estradiol in maintaining homeostasis of female connective tissue.     

Effects of long-term immobilization and recovery on human triceps surae and collagen turnover in the Achilles tendon in patients with healing ankle fracture.

The aim of the present study was to analyze how human tendon connective tissue responds to an approximately 7-wk period of immobilization and a remobilization period of a similar length, in patients with unilateral ankle fracture, which is currently unknown. Calf muscle cross-sectional area (CSA) decreased by 15% (5,316 to 4,517 mm2) and strength by 54% (239 to 110 N.m) in the immobilized leg after 7 wk. During the 7-wk remobilization, the CSA increased by 9% (to 4,943 mm2) and strength by 37% (to 176 Nm). Achilles tendon CSA did not change significantly during either immobilization or remobilization. Local collagen turnover was measured as the peritendinous concentrations of NH2-terminal propeptide of type I collagen (PINP) and COOH-terminal telopeptide region of type I collagen (ICTP), markers thought to be indexes of type I collagen synthesis and degradation, respectively. Both markers were increased (PINP: 257 vs. 56 ng/ml; ICTP: 9.8 vs. 2.1 microg/l) in the immobilized leg compared with the control leg after the 7 wk of immobilization, and levels decreased again in the immobilized leg during the recovery period (PINP: 103 vs. 44 ng/ml; ICTP: 4.2 vs. 1.9 microg/l). A significant reduction in calf muscle CSA and strength was found in relation to 7 wk of immobilization. Immobilization increased both collagen synthesis and degradation in tendon near tissue. However, it cannot be excluded that the facture of the ankle in close proximity could have affected these data. Remobilization increased muscle size and strength and tendon synthesis and degradation decreased to baseline levels. These dynamic changes in tendon connective tissue turnover were not associated with macroscopic changes in tendon size.     

Tendon collagen synthesis at rest and after exercise in women.

In general, there is a higher incidence of musculoskeletal injuries during physical activity in women than in men. We hypothesized that in women rates of tendon collagen synthesis would be lower than in men at rest and after exercise, especially in the later luteal phase when estrogen and progesterone concentrations are higher than the early follicular phase. We studied tendon collagen fractional synthesis rate (FSR) in 15 young, healthy female subjects in either the early follicular (n = 8) or the late luteal phase (n = 7) 72 h after an acute bout of one-legged exercise (60 min kicking at 67% workload maximum) (72 h) and compared the results with those previously obtained for men. Samples were taken from the patellar tendon in both the exercised and rested legs to determine collagen FSR by the incorporation of [15N]proline into tendon collagen hydroxyproline. There was no effect of menstrual phase on tendon collagen synthesis either at rest or after exercise. However, there was a significant difference between women and men at rest (women = 0.025 +/- 0.002%/h, men = 0.045 +/- 0.008%/h; P < 0.05) and 72 h after exercise (women = 0.027 +/- 0.005%/h; men = 0.058 +/- 0.008%/h). Furthermore, rest and 72-h tendon collagen synthesis were not different in women, whereas in men tendon collagen synthesis remained significantly elevated 72 h after exercise. It is concluded that both in the resting state and after exercise, tendon collagen FSR is lower in women than in men, which may contribute to a lower rate of tissue repair after exercise.     

Short-term immobilization and recovery affect skeletal muscle but not collagen tissue turnover in humans

Not much is known about the effects of immobilization and subsequent recovery on tendon connective tissue. In the present study, healthy young men had their nondominant leg immobilized for a 2-wk period, followed by a recovery period of the same length. Immobilization resulted in a mean decrease of 6% (5,413 to 5,077 mm(2)) in cross-sectional area (CSA) of the triceps surae muscles and a mean decrease of 9% (261 to 238 N.m) in strength of the immobilized calf muscles. Two weeks of recovery resulted in a 6% increased in CSA (to 5,367 mm(2)), whereas strength remained suppressed (240 N.m). No difference in Achilles tendon CSA was detected between the two legs at any time point. Local tendon collagen synthesis, measured as the peritendinous concentrations of PINP (NH(2)-terminal propeptide of type I collagen; indirect marker for collagen synthesis), was unchanged after 2 wk of immobilization. However, peritendinous levels of PINP were significantly elevated in the immobilized leg (15 to 139 ng/ml) following 2 wk of remobilization compared with preimmobilization levels. In contradiction hereto, systemic concentrations of PINP remained unchanged throughout the study. Immobilization reduced muscle size and strength, while tendon size and collagen turnover were unchanged. While recovery resulted in an increase in muscle size, strength was unchanged. No significant difference in tendon size could be detected between the two legs after 2 wk of recovery, although collagen synthesis was increased in the previously immobilized leg. Thus 2 wk of immobilization are sufficient to induce significant changes in muscle tissue, whereas tendon tissue seems to be more resistant to short-term immobilization.     

Interleukin-6: a growth factor stimulating collagen synthesis in human tendon

Human connective tissue, e.g., tendon, responds dynamically to physical activity, with collagen synthesis being increased after both acute and prolonged exercise or training. Markers of collagen synthesis and degradation as well as concentration of several potential growth factors have been shown to increase markedly in the peritendinous tissue around the human Achilles tendon following exercise. Of these potential growth factors interleukin-6 (IL-6) showed the largest fold increase, suggesting that IL-6 may be involved in transforming mechanical loading into collagen synthesis in human tendon tissue. In the present study the tissue levels of type I collagen turnover markers [procollagen type I NH(2)-terminal propeptide (PINP) and C-OOH terminal telopeptide of type I collagen (ICTP)] were measured by the use of microdialysis in peritendinous tissue of the Achilles tendon in 14 male volunteers, who had recombinant human IL-6 (rhIL-6) infused into the peritendinous tissue of the Achilles' tendon in one leg, with the other leg serving as control. Subjects were randomly assigned to either a resting group or an exercise group performing a 1-h treadmill run (12 km/h, 2% uphill) before infusion. In addition to IL-6, serum concentrations of collagen turnover markers PINP, ICTP, and COOH-terminal telopeptide of type I collagen (ICTX) were measured. The peritendinous concentration of PINP rose markedly in response to rhIL-6 infusion in both the exercise and the rest group, demonstrating that infusion of IL-6 significantly stimulates collagen synthesis in the peritendinous tissue in humans. Exercise alone did not result in an increased collagen synthesis. This indicates that IL-6 is involved in the collagen synthesis and supports the hypothesis that IL-6 is an important growth factor of the connective tissue in healthy human tendons.     

Muscle fibre length-to-moment arm ratios in the human lower limb determined in vivo

The purpose of this study was to quantify in vivo the fibre length (L)-to-moment arm (d) ratio (L/d) in the major ankle plantarflexors and knee extensors of 21 healthy men. Measurements of L were taken in the gastrocnemius medialis, gastrocnemius lateralis, soleus, vastus lateralis and vastus intermedius muscles using ultrasound scanning. Measurements of d were taken in the Achilles tendon (d(AT)) and patellar tendon (d(PT)) using magnetic resonance imaging. The relations between (a) L in each ankle plantarflexor muscle and d(AT), (b) L in each knee extensor muscle and d(PT), and (c) d(AT) and d(PT,) were analyzed with Pearson correlation coefficients. There was no significant relation (P>0.05) between any of the above parameters, with the correlation coefficient values ranging from -0.2 to 0.29. These results contradict previous findings that L scales with d, indicating that skeletal size differences between individuals may not always be associated with predictable differences in muscle architecture. This needs to be accounted for when information about the L/d ratio of a given muscle-joint in a given individual is required, as for example is the case when assessing the suitability of a potential donor muscle in surgical tendon transfer.     

Vastus medialis myocutaneous and myocutaneous-tendinous composite flaps

This report describes a new myocutaneous territory and introduces a new myocutaneous flap based on the vastus medialis muscle. Dissection, arterial dye perfusion, and specimen angiography of 32 fresh cadaver legs defined a vastus medialis myocutaneous territory directly overlying the muscle and also defined a segment of quadriceps femoris tendon vascularized by the muscle. This vascular unit provides a myocutaneous flap for closure of anterior knee defects. This flap can also be designed as a composite myocutaneous-tendinous flap by inclusion of the vascularized quadriceps femoris tendon segment, which allows reconstruction of missing patellar tendon segments. The distal advancement flap design with retention of motor innervation preserves vastus medialis contribution to knee extension. Clinical applications of vastus medialis myocutaneous and myocutaneous-tendinous flaps are illustrated by their use in three patients with knee defects and patellar tendon losses. The potential value of vascularized tendon (versus vascular free tendon grafts) for patellar tendon reconstruction is discussed.     

Maturational alterations in gap junction expression and associated collagen synthesis in response to tendon function

Energy-storing tendons including the equine superficial digital flexor tendon (SDFT) contribute to energetic efficiency of locomotion at high-speed gaits, but consequently operate close to their physiological strain limits. Significant evidence of exercise-induced microdamage has been found in the SDFT which appears not to exhibit functional adaptation; the degenerative changes have not been repaired by the tendon fibroblasts (tenocytes), and are proposed to accumulate and predispose the tendon to rupture during normal athletic activity. The anatomically opposing common digital extensor tendon (CDET) functions only to position the digit, experiencing significantly lower levels of strain and is rarely damaged by exercise. A number of studies have indicated that tenocytes in the adult SDFT are less active in collagen synthesis and turnover than those in the immature SDFT or the CDET. Gap junction intercellular communication (GJIC) is known to be necessary for strain-induced collagen synthesis by tenocytes. We postulate therefore that expression of GJ proteins connexin 43 and 32 (Cx43; Cx32), GJIC and associated collagen expression levels are high in the SDFT and CDET of immature horses, when the SDFT in particular grows significantly in cross-sectional area, but reduce significantly during maturation in the energy-storing tendon only. The hypothesis was tested using tissue from the SDFT and CDET of foetuses, foals, and young adult Thoroughbred horses. Cellularity and the total area of both Cx43 and Cx32 plaques/mm² of tissue reduced significantly with maturation in each tendon. However, the total Cx43 plaque area per tenocyte significantly increased in the adult CDET. Evidence of recent collagen synthesis in the form of levels of neutral salt-soluble collagen, and collagen type I mRNA was significantly less in the adult compared with the immature SDFT; procollagen type I amino-propeptide (PINP) and procollagen type III amino-propeptide (PIIINP) levels per mm² of tissue and PINP expression per tenocyte also decreased with maturation in the SDFT. In the CDET PINP and PIIINP expression per tenocyte increased in the adult, and exceeded those in the adult SDFT. The level of PINP per mm² was greater in the adult CDET than in the SDFT despite the higher cellularity of the latter tendon. In the adult SDFT, levels of PIIINP were greater than those of PINP, suggesting relatively greater synthesis of a weaker form of collagen previously associated with microdamage. Tenocytes in monolayers showed differences in Cx43 and Cx32 expression compared with those in tissue, however there were age- and tendon-specific phenotypic differences, with a longer time for 50% recovery of fluorescence after photobleaching in adult SDFT cells compared with those from the CDET and immature SDFT. As cellularity reduces following growth in the SDFT, a failure of the remaining tenocytes to show a compensatory increase in GJ expression and collagen synthesis may explain why cell populations are not able to respond to exercise and to repair microdamage in some adult athletes. Enhancing GJIC in mature energy-storing tendons could provide a strategy to increase the cellular synthetic and reparative capacity.     

A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly

This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of L-[ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 +/- 0.005%/h; post-EAA: 0.063 +/- 0.007%/h) and the 41% (basal: 0.036 +/- 0.004%/h; post-EAA: 0.051 +/- 0.007%/h) Leu young groups (P < 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 +/- 0.003%/h; post-EAA: 0.049 +/- 0.006%/h; P > 0.05) but did increase following ingestion of 41% Leu EAA (basal: 0.038 +/- 0.007%/h; post-EAA: 0.056 +/- 0.008%/h; P < 0.05). Similar to the FSR responses, the mean response of muscle phenylalanine net balance, a reflection of muscle protein balance, was improved (P < 0.05) in all groups, with the exception of the 26% Leu elderly group. We conclude that increasing the proportion of leucine in a mixture of EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects.     

Synergistic promoting effects of bone morphogenetic protein 12/connective tissue growth factor on functional differentiation of tendon derived stem cells and patellar tendon window defect regeneration

Current study investigated bone morphogenetic protein 12 (BMP12) and connective tissue growth factor (CTGF) activate tendon derived stem cells (TDSCs) tenogenic differentiation, and promotion of injured tendon regeneration. TDSCs were transfected with BMP12 and CTGF via recombinant adenovirus (Ad) infection. Gene transfection efficiency, cell viability and cytotoxicity, tenogenic gene expression, collagen I/III synthesis were evaluated in vitro. For the in vivo study, the transfected cells were transplanted into the rat patellar tendon window defect. At weeks 2 and 8 of post-surgery, the repaired tendon tissues were harvested for histological and biomechanical examinations. The transfected TDSCs revealed relatively stable transfection efficiency (80–90%) with active cell viability means while rare cytotoxicity in each group. During days 1 and 5, BMP12 and CTGF transfection caused tenogenic differentiation genes activation in TDSCs: type I/III collagen, tenascin-C, and scleraxis were all up-regulated, whereas osteogenic, adipogenic, and chondrogenic markers were all down-regulated respectively. In addition, BMP12 and CTGF overexpression significantly promote type I/III collagen synthesis. After in vivo transplantation, at 2 and 8 weeks post-surgery, BMP12, CTGF and co-transfection groups showed more integrated tendon tissue structure versus control, meanwhile, the ultimate failure loads and Young’s were all higher than control. Remarkably, at 8 weeks post-surgery, the biomechanical properties of co-transfection group was approaching to normal rat patellar tendon, moreover, the ratio of type III/I collagen maintained about 20% in each transfection group, meanwhile, the type I collagen were significantly increased with co-transfection treatment. In conclusion, BMP12 and CTGF transfection stimulate tenogenic differentiation of TDSCs. The synergistic effects of simultaneous transfection of both may significantly promoted rat patellar tendon window defect regeneration.     

Expression of insulin-like growth factor I, insulin-like growth factor binding proteins, and collagen mRNA in mechanically loaded plantaris tendon.

Insulin-like growth factor I (IGF-I) is known to exert an anabolic effect on tendon fibroblast production of collagen. IGF-I's regulation is complex and involves six different IGF binding proteins (IGFBPs). Of these, IGFBP-4 and -5 could potentially influence the effect of IGF-I in the tendon because they both are produced in fibroblast; however, the response of IGFBP-4 and -5 to mechanical loading and their role in IGF-I regulation in tendinous tissue are unknown. A splice variant of IGF-I, mechano-growth factor (MGF) is upregulated and known to be important for adaptation in loaded muscle. However, it is not known whether MGF is expressed and upregulated in mechanically loaded tendon. This study examined the effect of mechanical load on tendon collagen mRNA in relation to changes in the IGF-I systems mRNA expression. Data were collected at 2, 4, 8 and 16 days after surgical removal of synergistic muscle to the plantaris muscle of the rat, thus increasing the load to plantaris muscle and tendon. Nearly a doubling of the tendon mass was observed after 16 days of loading. A rapid rise in tendon procollagen III mRNA was seen after 2 days whereas the increase in procollagen I mRNA was significant from day 8. MGF was expressed and upregulated in loaded tendon tissue with a faster response than IGF-I, which was increased from day 8. Finally, IGFBP-4 mRNA was increased with a time pattern similar to procollagen III, whereas IGFBP-5 decreased at day 8. In conclusion, loading of tendon tissue results in an upregulation of IGF-I, IGFBP-4, and procollagen and is associated with an increase in tendon mass. Also, MGF is expressed with an early upregulation in loaded tendon tissue. We suggest that the IGF-I system could be involved in collagen synthesis in tendon in response to mechanical loading.     

Collagen synthesis in human musculoskeletal tissues and skin

We have developed a direct method for the measurement of human musculoskeletal collagen synthesis on the basis of the incorporation of stable isotope-labeled proline or leucine into protein and have used it to measure the rate of synthesis of collagen in tendon, ligament, muscle, and skin. In postabsorptive, healthy young men (28 +/- 6 yr) synthetic rates for tendon, ligament, muscle, and skin collagen were 0.046 +/- 0.005, 0.040 +/- 0.006, 0.016 +/- 0.002, and 0.037 +/- 0.003%/h, respectively (means +/- SD). In postabsorptive, healthy elderly men (70 +/- 6 yr) the rate of skeletal muscle collagen synthesis is greater than in the young (0.023 +/- 0.002%/h, P < 0.05 vs. young). The rates of synthesis of tendon and ligament collagen are similar to those of mixed skeletal muscle protein in the postabsorptive state, whereas the rate for muscle collagen synthesis is much lower in both young and elderly men. After nutrient provision, collagen synthesis was unaltered in tendon and skeletal muscle, remaining at postabsorptive values (young: tendon, 0.045 +/- 0.008%/h; muscle, 0.016 +/- 0.003%/h; elderly: muscle, 0.024 +/- 0.003%/h). These results demonstrate that the rate of human musculoskeletal tissue collagen synthesis can be directly and robustly measured using stable isotope methodology.     

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.     

Human muscle protein turnover--why is it so variable?

We undertook a comprehensive review of the literature to unravel the nature of the variability in the reported rate of human muscle protein synthesis. We analyzed the results from studies that report the protein fractional synthesis rate (FSR) in the vastus lateralis in healthy, nonobese, untrained adults ≤50 yr of age in the postabsorptive state at rest by using the primed, constant tracer amino acid infusion method according to experimental design characteristics. We hypothesized that if the variability is methodological (rather than physiological) in nature, systematic clustering of FSR values would be evident, and outliers would become apparent. Overall, as expected, the mixed muscle protein FSR values were significantly (P < 0.001) greater when the muscle vs. the plasma free amino acid enrichment is used as the surrogate precursor pool enrichment, and the average mixed muscle protein FSR values were significantly greater (P = 0.05) than the myofibrillar/myosin heavy chain FSR values. The within-study variability (i.e., population variance) was somewhat smaller in studies that used plasma amino acid/ketoacid enrichments vs. muscle free amino acid enrichment (～24 vs. ～31%), but this was not apparent in all circumstances. Furthermore, the between-study consistency of measured FSR values (i.e., interquartile range) was inversely correlated with the average duration between biopsies. Aside from that, the variation in reported FSR values could not be explained by differences in the experimental design and analytical methods, and none of the most commonly used approaches stood out as clearly superior in terms of consistency of results and/or within-study variability. We conclude that the variability in reported values is in part due to 1) differences in experimental design (e.g., choice of precursor pool) and 2) considerable within-subject variability. The summary of the results from our analysis can be used as guidelines for "normal" average basal FSR values at rest in healthy adults.     

Adaptation of bone and tendon to prolonged hindlimb suspension in rats

The rat hindlimb suspension model was used to ascertain the importance of ground reaction forces in maintaining bone and tendon homeostasis. Young female Sprague-Dawley rats were randomly assigned to either a suspended or a nonsuspended group. After 28 days, femur bones and patellar tendons were obtained for morphological and biochemical analyses. Prolonged suspension induced a significant change in the geometric configuration of the femur middiaphysis by increasing the minimum diameter (12%) without any significant alterations in cortical area, density, mineral, and collagen concentrations. Femur wet weight, length, DNA, and uronic acid concentrations of suspended animals were not significantly different from bones of nonsuspended rats. However, the collagen and proteoglycan concentrations in patellar tendons of suspended rats were 28% lower than the concentrations of matrix proteins in tissues obtained from nonsuspended animals. These data suggest that elimination of ground reaction forces induces alterations in tendon composition and femur diaphyseal shape by changing regional rates in bone remodeling and localized tendon strain. Therefore it appears that ground reaction forces are an important factor in the maintenance of cortical bone and patellar tendon homeostasis during weight-bearing conditions.     

Effect of anti-inflammatory medication on the running-induced rise in patella tendon collagen synthesis in humans

NSAIDs are widely used in the treatment of inflammatory diseases as well as of tendon diseases associated with pain in sports and labor. However, the effect of NSAID intake, and thus blockade of PGE(2) production, on the tendon tissue adaptation is unknown. The purpose of the present study was to elucidate the possible effects of NSAID intake on healthy tendon collagen turnover in relation to a strenuous bout of endurance exercise. Fifteen healthy young men were randomly assigned into two experimental groups, with one group receiving indomethacin (oral 2 × 100 mg Confortid daily for 7 days; NSAID; n = 7) and a placebo group (n = 8). Both groups were exposed to a prolonged bout of running (36 km). The collagen synthesis NH?-terminal propeptide of type I (PINP) and PGE? concentrations were measured before and 72 h following the run in the patella tendon by microdialysis. The peritendinous concentrations of PINP increased significantly in the placebo group as a result of the run, as shown previously. PGE? levels were significantly decreased 72 h after the run compared with basal levels in the subjects treated with NSAID and unchanged in the placebo group. The NSAID intake abolished the adaptive increase in collagen synthesis in the patella tendon found in the placebo group in response to the prolonged exercise (P < 0.05). The present study demonstrates that intake of NSAID decreased interstitial PGE? and abolished the exercise-induced adaptive increase in collagen synthesis in human tendons.     

Protein anabolic effects of insulin and IGF-I in the ovine fetus

We determined the effect of insulin and/or recombinant human (rh)IGF-I infusion on ovine fetal phenylalanine kinetics, protein synthesis, and phenylalanine accretion. The chronically catheterized fetal lamb model was used at 130 days gestation. All studies were performed while fetal glucose and amino acid concentrations were held constant. Experimental infusates were 1). saline, 2). rhIGF-I plus a replacement dose of insulin (40 nmol), 3). insulin (890 mIU/h), and 4). IGF-I plus insulin (40 nmol IGF-I/h and 890 mIU insulin/h). Both hormones increased glucose and amino acid utilization, with insulin having a greater effect. The major effect on phenylalanine kinetics was a pronounced fall in phenylalanine hydroxylation, again with insulin having the greatest effect. Whole body protein breakdown was not significantly altered by either hormone; whole body protein synthesis was significantly increased during the combined infusion. Protein accretion was increased by both hormones, with the greatest increase during combined infusion. The fractional synthetic rate (FSR) of circulating albumin was increased by IGF-I but not by insulin. Both hormones significantly increased skeletal muscle FSR without a synergistic effect. The anabolic effects of insulin and IGF-I were more pronounced in these studies than in previous studies where amino acid concentrations were not maintained. The present data also suggest that insulin and IGF-I promote fetal growth through distinct, organ-specific mechanisms.     

Characteristics of bone tissue metabolism in adolescents with undifferentiated connective tissue dysplasia

Biochemical markers of bone metabolism, including osteocalcin, total aminoterminal propeptide type I collagen (PINP), and the product of degradation of carboxy-terminal telopeptide type I collagen (β-CrossLaps) were studied in 17 adolescents 11–14 years of age with undifferentiated connective tissue dysplasia (UDCT). Decreased serum concentrations of bone formation markers (PINP and osteocalcin) against the background of normal levels of the bone resorption marker (β-CrossLaps) indicated that the processes of bone remodeling were disturbed and characterized by low-intensity bone-tissue formation with the relative predominance of resorption. The detected bone metabolism disturbances contributed to the development of osteopenia, which gives us grounds to include adolescents with UDCT to the risk group for early-onset osteoporosis.     

Effect of implanting a soft tissue autograft in a central-third patellar tendon defect: biomechanical and histological comparisons

Previous studies by our laboratory have demonstrated that implanting a stiffer tissue engineered construct at surgery is positively correlated with repair tissue stiffness at 12 weeks. The objective of this study was to test this correlation by implanting a construct that matches normal tissue biomechanical properties. To do this, we utilized a soft tissue patellar tendon autograft to repair a central-third patellar tendon defect. Patellar tendon autograft repairs were contrasted against an unfilled defect repaired by natural healing (NH). We hypothesized that after 12 weeks, patellar tendon autograft repairs would have biomechanical properties superior to NH. Bilateral defects were established in the central-third patellar tendon of skeletally mature (one year old), female New Zealand White rabbits (n?=?10). In one limb, the excised tissue, the patellar tendon autograft, was sutured into the defect site. In the contralateral limb, the defect was left empty (natural healing). After 12 weeks of recovery, the animals were euthanized and their limbs were dedicated to biomechanical (n?=?7) or histological (n?=?3) evaluations. Only stiffness was improved by treatment with patellar tendon autograft relative to natural healing (p?=?0.009). Additionally, neither the patellar tendon autograft nor natural healing repairs regenerated a normal zonal insertion site between the tendon and bone. Immunohistochemical staining for collagen type II demonstrated that fibrocartilage-like tissue was regenerated at the tendon-bone interface for both repairs. However, the tissue was disorganized. Insufficient tissue integration at the tendon-to-bone junction led to repair tissue failure at the insertion site during testing. It is important to re-establish the tendon-to-bone insertion site because it provides joint stability and enables force transmission from muscle to tendon and subsequent loading of the tendon. Without loading, tendon mechanical properties deteriorate. Future studies by our laboratory will investigate potential strategies to improve patellar tendon autograft integration into bone using this model.     

绝经后骨质疏松症患者血清LECT2水平的临床意义及其预测价值分析

摘要 目的：探讨绝经后骨质疏松症患者血清白细胞衍生趋化因子2（LECT2）水平的临床意义及其预测价值。方法：选择2020年1月～2022年1月湖南师范大学第一附属医院收治的绝经后骨质疏松症患者125例作为研究组,另选取同期体检的绝经后健康女性志愿者120例作为对照组。比较两组血清LECT2水平,并分析血清LECT2水平与腰椎和股骨颈骨密度（BMD）及骨代谢相关指标的相关性;应用受试者工作特征（ROC）曲线分析血清LECT2对绝经后骨质疏松症患者的预测价值。结果：研究组血清LECT2、骨钙素（OC）、I型原胶原N端前肽（PINP）、 I型胶原交联C末端肽（S-CTX）显著高于对照组,腰椎和股骨颈BMD显著低于对照组（P<0.05）。Pearson相关分析显示,绝经后骨质疏松症患者血清LECT2水平与OC、PINP、S-CTX水平呈正相关（P<0.05）,与腰椎和股骨颈BMD呈负相关（P<0.05）。ROC曲线分析显示,血清LECT2、OC、PINP、S-CTX联合检验对绝经后骨质疏松症患者的预测价值的曲线下面积（AUC）为0.856,大于各单一指标预测。结论：绝经后骨质疏松症女性血清LECT2水平升高,其水平与骨代谢指标OC、PINP、S-CTX水平呈正相关,与腰椎BMD和股骨颈BMD呈负相关,血清LECT2联合OC、PINP、S-CTX对绝经后骨质疏松症患者的预测价值较高。