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1.
Despite the continued presence of growth plates in aged rats, longitudinal growth no longer occurs. The aims of this study were to understand the reasons for the cessation of growth. We studied the growth plates of femurs and tibiae in Wistar rats aged 62-80 weeks and compared these with the corresponding growth plates from rats aged 2-16 weeks. During skeletal growth, the heights of the plates, especially that of the hypertrophic zone, reflected the rate of bone growth. During the period of decelerating growth, it was the loss of large hydrated chondrocytes that contributed most to the overall decrease in the heights of the growth plates. In the old rats we identified four categories of growth plate morphology that were not present in the growth plates of younger rats: (a). formation of a bone band parallel to the metaphyseal edge of the growth plate, which effectively sealed that edge; (b). extensive areas of acellularity, which were resistant to resorption and/or remodeling; (c). extensive remodeling and bone formation within cellular regions of the growth plate; and (d). direct bone formation by former growth plate chondrocytes. These processes, together with a loss of synchrony across the plate, would prevent further longitudinal expansion of the growth plate despite continued sporadic proliferation of chondrocytes.  相似文献   

2.
The injured growth plate cartilage is often repaired by bony tissue, resulting in impaired bone growth in children. Bone morphogenic proteins (BMPs) are important for bone fracture repair, and as a step to characterize potential involvement of BMPs in bony repair of injured growth plate, expression of BMPs and receptors (BMP-R) was examined by quantitative RT-PCR and immunohistochemistry in rat injured tibial growth plate. During the inflammatory response on day 1, slightly increased expression of BMP-3, BMP-4, BMP-R1a, and BMP-R2 was observed, with immunostaining seen among inflammatory cells at the injury site. During mesenchymal infiltration and osteogenic responses on days 3-14, moderately increased expression of BMP-2, -3, -4, -7, and BMP-R1a was found, with immunostaining observed among infiltrated mesenchymal cells and differentiated osteoblasts lining bony trabeculae. During maturation phase on days 14-25, only BMP-7 was seen upregulated slightly and was localized in osteoblasts and marrow cells at the injury site. The temporospatial expression of BMPs and receptors at the injured growth plate suggests potential involvement of BMP-3 and -4 in regulating the inflammatory response or as its mediators in modulating downstream events, and BMP-2, -3, -4, and -7 in the fibrogenic and osteogenic responses, and BMP-7 in bone remodeling at the injured growth plate.  相似文献   

3.
Regeneration of missing body parts in model organisms provides information on the mechanisms underlying the regeneration process. The aim here is to use ctenophores to investigate regeneration of their giant ciliary swimming plates. When part of a row of comb plates on Mnemiopsis is excised, the wound closes and heals, greatly increasing the distance between comb plates near the former cut edges. Video differential interference contrast (DIC) microscopy of the regeneration of new comb plates between widely separated plates shows localized widenings of the interplate ciliated groove (ICG) first, followed by growth of two opposing groups of comb plate cilia on either side. The split parts of a new plate elongate as their bases extend laterally away from the ICG widening and continue ciliogenesis at both ends. The split parts of a new plate grow longer and move closer together into the ICG widening until they merge into a single plate that interrupts the ICG in a normal manner. Video DIC snapshots of dissected gap preparations 1.5–3‐day postoperation show that ICG widenings and/or new plates do not all appear at the same time or with uniform spacing within a gap: the lengths and distances between young plates in a gap are quite variable. Video stereo microscopy of intact animals 3–4 days after the operation show that all the new plates that will form in a gap are present, fairly evenly spaced and similar in length, but smaller and closer together than normal. Normal development of comb plates in embryos and growing animals is compared to the pattern of comb plate regeneration in adults. Comb plate regeneration differs in the cydippid Pleurobrachia that lacks ICGs and has a firmer mesoglea than Mnemiopsis. This study provides a morphological foundation for histological, cellular, and molecular analysis of ciliary regeneration in ctenophores. J. Morphol. 2011. © 2011 Wiley Periodicals, Inc.  相似文献   

4.
Acute pancreatitis leads to pancreatic damage followed by subsequent regeneration. The aim of our study was to evaluate the presence of growth factors in the course of spontaneous pancreatic regeneration after ischemia/reperfusion (I/R)-induced pancreatitis. METHODS: In rats, I/R was evoked by clamping of splenic artery for 30 min followed by reperfusion. Rats were sacrificed 1, 5, 12 h or 1, 2, 3, 5, 7, 9 or 21 days after removal of vascular clips. Pancreatic blood flow (PBF), plasma lipase, interleukin-1beta (IL-1beta), interleukin-10, pancreatic cells proliferation and morphological signs of pancreatitis were determined. Pancreatic presence of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta type II receptor (TGFbeta RII) was detected by immunohistochemisty. RESULTS: Exposure to I/R led to the development of acute necrotizing pancreatitis followed by regeneration. Morphological features showed maximal pancreatic damage between the 1(st) and 2(nd) day of reperfusion. It was correlated with a maximal increase in plasma lipase, and pro-inflammatory IL-1beta concentration, as well as, a reduction in PBF and pancreatic DNA synthesis. I/R increased FGF-2 content in pancreatic acinar cells between the 12(th) and 24(th) h, and between 5(th) and 9(th) day of reperfusion. At the 2(nd) day the presence of FGF-2 in pancreatic acinar cells was reduced. After I/R PDGF-A appeared in pancreatic vessels from the 12(th) h to 5 (th) day of reperfusion. PDGF-A was not observed in pancreatic acinar cells in the control or in I/R group. In pancreatic ducts, the presence of PDGF-A was reduced between the 1(st) and 3(rd), and between 7(th) and 9(th) day of reperfusion. In acinar cells, VEGF content was increased after I/R at the time between the 1(st) and 24(th) h, and between 3(rd) and 7(th) day of reperfusion. At the 2(nd) day of reperfusion, VEGF was not detected in the pancreatic acinar cells. Moreover, VEGF was found in the inflammatory infiltration, in the tubular complexes between the 2(nd) and 5(th) day, and in granulation tissue at the 9(th) day of reperfusion. In pancreatic acinar cells, I/R caused an increase in TGFbeta RII presence between the 5(th) and 24(th) h, and between 7(th) and 9(th) day of reperfusion. Between the 2(nd) and 5(th) day of reperfusion the acinar presence of TGFbeta RII was reduced. In the pancreatic ducts, the presence of TGFbeta RII was increased after I/R from the 1(st) h to 9(th) day of observation. Four weeks after induction of acute pancreatitis, the pancreatic regeneration was completed and the presence of growth factors tested returned to control value. CONCLUSIONS: The presence of FGF, VEGF, PDGF-A and TGFbeta RII is modified in the course of I/R-induced acute pancreatitis. Maximal content of FGF, VEGF and TGFbeta RII has been observed in early stage of pancreatic regeneration suggesting the involvement these factors in pancreatic recovery.  相似文献   

5.
The purpose of this study was to examine the effect of Lactosorb absorbable plates on bone healing across cranial bone defects in the rabbit skull. Two 10-mm diameter parietal skull defects were created in each of 20 rabbits, with one defect being placed on either side of the sagittal suture. In 10 rabbits, an absorbable plate was placed across both the inner and outer cortices of the left defect, and in the other 10 rabbits, an absorbable plate was placed across the outer cortex only of the left defect. The right defect always served as the control side, with no plate being placed across it. Rabbits were killed an average of 25 weeks postoperatively. Areas of reossification in the experimental and control defects of each rabbit were then measured, examined histologically, and compared. Growth across defects spanned by one plate was also compared with growth across defects spanned by two plates. Histologic and statistical analyses revealed no significant differences in reossification between the control and experimental defects in each animal and between the defects spanned by one versus two plates. This study suggests that these copolymer absorbable plates neither inhibit nor facilitate reossification across 10-mm diameter rabbit cranial defects.  相似文献   

6.
Twenty-seven male albino rats underwent hindlimb amputations through the lower femur or the midshaft of the tibiofibula on the tenth to 12th day of life. Amputation stumps were examined grossly and histologically in order to assess the significance of level and angle of transaction as determinants of subsequent growth and regeneration and to ascertain whether growth plates can regenerate following their complete excision. Amputees survived for 17-73 days. In order to exclude limbs which had been severed at or distal to the level of the growth plate, amputated limb segments either were cleared to transparency and inspected under low magnification or were sectioned serially and examined by using a compound microscope. Following amputations through the femur, the predominant response involved repair of the skeletal defect and healing of adjacent soft tissues (ten of 17 rats). Among five other animals the skeletal terminus was covered with a plate of cartilage which, in three, included areas of growth-plate architecture. Two additional transfemoral amputees regenerated incomplete growth plates, each overlying a single epicondylar surface, and one provided with a regenerated hemiepiphysis. Five of ten transtibiofibular amputees formed cartilage plates which covered the skeletal terminus in whole or in part and one regenerated an entire growth plate restricted to the distal fibula. It is concluded that angle and level of transection are not pivotal modifiers of growth and regeneration processes, and that distal growth plates may regenerate entirely or in part following their complete removal from the hindlimb.  相似文献   

7.
Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation.  相似文献   

8.
Bone grafting is used to enhance healing in osteotomies, arthrodesis, and multifragmentary fractures and to replace bony loss resulting from neoplasia or cysts. They are source of osteoprogenitor cells and induce bone formation and provide mechanical support for vascular and bone ingrowth. Autografts are used commonly but quantity of retrieved bone is limit. This study was designed to evaluate autograft and new xenograft (Bovine fetal growth plate) effects on bone healing process. Twenty male White New Zealand rabbits were used in this study. In autograft group the defect was filled by fresh autogenous cortical graft, in xenograft group the defect was filled by a segment of bovine fetal growth plate and was fixed by cercelage wire. Radiological, histopathological and biomechanical evaluations were performed blindly and results scored and analyzed statistically. Statistical tests did not support significant differences between two groups at the 14th and 28th postoperative day radiographically (P > 0.05). There was a significant difference for remodeling at the 42nd postoperative radiologically (P < 0.05). Xenograft was superior to autograft at the 56th postoperative day for radiological bone formation (P < 0.03). Histopathological and biomechanical evaluation revealed no significant differences between two groups. The results of this study indicate that satisfactory healing occurred in rabbit radius defect filled with calf fetal growth plate. Complications were not identified and healing was faster than cortical autogenous grafting. It was concluded that the use of calf fetal growth plate as a new xenograft is an acceptable alternative to cortical autogenous graft and could reduce the morbidity associated with harvesting autogenous graft during surgery.  相似文献   

9.
为研究不同半导体激光照射方法对周围神经损伤的影响,将96只家兔随机分为3周,6周,9周,12周4个观察期组,每个观察期组又随机分为不同照射方法的治疗组和对照组。建立动物模型后,各照射组在术后1d开始照射治疗,激光功率为10mw,每次照射10rain,每天一次,连续照射10d。照射治疗A组对准损伤神经吻合部位进行照射,照射治疗B组照射家兔L5、L6脊髓节段,照射治疗c组在对准吻合处进行照射同时还要照射L5、L6脊髓节段,对照组激光输出功率为零。实验结果表明低能量半导体激光照射能促进轴突再生,改善再生神经功能,以同时照射损伤周围神经部位和相应脊髓节段效果最为显著。  相似文献   

10.
Trans-resveratrol (RES), naturally produced by many plants, has a structure similar to synthetic estrogen diethylstilbestrol, but any effect on bone growth has not yet been clarified. Pre-pubertal ovary-intact New Zealand white rabbits received daily oral administration of either vehicle (control) or RES (200 mg/kg) until growth plate fusion occurred. Bone growth and growth plate size were longitudinally monitored by X-ray imaging, while at the endpoint, bone length was assessed by a digital caliper. In addition, pubertal ovariectomized (OVX) rabbits were treated with vehicle, RES or estradiol cypionate (positive control) for 7 or 10 weeks and fetal rat metatarsal bones were cultured in vitro with RES (0.03 µM–50 µM) and followed for up to 19 days. In ovary-intact rabbits, sixteen-week treatment with RES increased tibiae and vertebrae bone growth and subsequently improved final length. In OVX rabbits, RES delayed fusion of the distal tibia, distal femur and proximal tibia epiphyses and femur length and vertebral bone growth increased when compared with controls. Histomorphometrical analysis showed that RES-treated OVX rabbits had a wider distal femur growth plate, enlarged resting zone, increased number/size of hypertrophic chondrocytes, increased height of the hypertrophic zone, and suppressed chondrocyte expression of VEGF and laminin. In cultured fetal rat metatarsal bones, RES stimulated growth at 0.3 µM while at higher concentrations (10 μM and 50 μM) growth was inhibited. We conclude that RES has the potential to improve longitudinal bone growth. The effect was associated with a delay of growth plate fusion resulting in increased final length. These effects were accompanied by a profound suppression of VEGF and laminin expression suggesting that impairment of growth plate vascularization might be an underlying mechanism.  相似文献   

11.
Perlecan (Hspg2) is a heparan sulfate proteoglycan expressed in basement membranes and cartilage. Perlecan deficiency (Hspg2(-/-)) in mice and humans causes lethal chondrodysplasia, which indicates that perlecan is essential for cartilage development. However, the function of perlecan in endochondral ossification is not clear. Here, we report the critical role of perlecan in VEGF signaling and angiogenesis in growth plate formation. The Hspg2(-/-) growth plate was significantly wider but shorter due to severely impaired endochondral bone formation. Hypertrophic chondrocytes were differentiated in Hspg2(-/-) growth plates; however, removal of the hypertrophic matrix and calcified cartilage was inhibited. Although the expression of MMP-13, CTGF, and VEGFA was significantly upregulated in Hspg2(-/-) growth plates, vascular invasion into the hypertrophic zone was impaired, which resulted in an almost complete lack of bone marrow and trabecular bone. We demonstrated that cartilage perlecan promoted activation of VEGF/VEGFR by binding to the VEGFR of endothelial cells. Expression of the perlecan transgene specific to the cartilage of Hspg2(-/-) mice rescued their perinatal lethality and growth plate abnormalities, and vascularization into the growth plate was restored, indicating that perlecan in the growth plate, not in endothelial cells, is critical in this process. These results suggest that perlecan in cartilage is required for activating VEGFR signaling of endothelial cells for vascular invasion and for osteoblast migration into the growth plate. Thus, perlecan in cartilage plays a critical role in endochondral bone formation by promoting angiogenesis essential for cartilage matrix remodeling and subsequent endochondral bone formation.  相似文献   

12.
13.
Mammalian metapodials (metacarpals and metatarsals), unlike most long bones, form a single growth plate, and undergo longitudinal growth at only one end. The growth dynamics of non-mammalian tetrapod metapodials have not been systematically examined in order to determine if unidirectional growth is unique to mammals. Here we compare murine metapodial ossification in growth stages that parallel those of embryonic, juvenile and subadult American alligators (Alligator mississippiensis). Safranin O staining was used for qualitative histology, and chondrocyte differentiation and proliferation were assessed via immunohistochemistry for type X collagen and proliferative cell nuclear antigen (PCNA). We establish that growth plates form at both ends of alligator metapodials and are maintained in the subadult. PCNA results show that alligators and mice share common patterns of chondrocyte proliferation during growth plate formation. In addition, while alligators and mice differ initially in the degree of organization and pace of chondrocyte differentiation, these parameters are largely similar in established growth plates. However, the replacement of cartilage by bone is highly irregular throughout growth in the alligator, in contrast to the more uniform process in the mouse. These results indicate that while alligators and mammals share common mechanisms of chondrocyte regulation, they differ substantially in their processes of ossification. Phylogenetic analysis indicates that the direct ossification of one epiphysis and reliance on a single growth plate is a derived character (synapomorphy) in therian mammals and likely indicates an adaptation for erect quadrupedal gait.  相似文献   

14.
Growth plates are highly inhomogeneous in morphology and composition. Mechanical loading can modulate longitudinal bone growth, though the mechanisms underlying this mechanobiology are poorly understood. The proximal tibial growth plates of six rats were tested in vitro under uniaxial compression to 5% strain, and confocal microscopy was used to track and capture images of fluorescently labeled cell nuclei with increasing applied strains. The local strain patterns through the growth plate thickness were quantified using texture correlation analysis. The technique of texture correlation analysis was first validated by comparing theoretical simulated strain maps generated from numerically distorted images. The texture correlation algorithm was sensitive to the grid size superimposed on the original image, but remained insensitive to parameters related to the size of the final image mask, which was searched by the correlation algorithm for each grid point of the original image. Within the growth plate, experimental strain distributions were non-uniform in all six specimens. Growth plates were mostly under compression strains. The strain distributions differed among the histomorphological zones of the growth plate, which was most obvious in specimens with regular growth plate shape: higher compressive strains (4-8 times higher than the applied 5% strain) were located mainly in regions overlapping the reserve and hypertrophic zones with lower compressive strains in the proliferative zone. This study documents the non-uniform mechanical behavior of growth plate across its three histological zones when exposed to compression. Further investigation is required to establish the significance of non-uniform strain fields during growth in vivo.  相似文献   

15.
Jin J  Zhao Y  Tan X  Guo C  Yang Z  Miao D 《PloS one》2011,6(6):e21005
To develop an effective therapeutic strategy for cardiac regeneration using bone marrow mesenchymal stem cells (BM-MSCs), the primary mouse BM-MSCs (1(st) BM-MSCs) and 5(th) passage BM-MSCs from β-galactosidase transgenic mice were respectively intramyocardially transplanted into the acute myocardial infarction (AMI) model of wild type mice. At the 6(th) week, animals/tissues from the 1(st) BM-MSCs group, the 5(th) passage BM-MSCs group, control group were examined. Our results revealed that, compared to the 5(th) passage BM-MSCs, the 1(st) BM-MSCs had better therapeutic effects in the mouse MI model. The 1(st) BM-MSCs maintained greater differentiation potentials towards cardiomocytes or vascular endothelial cells in vitro. This is indicated by higher expressions of cardiomyocyte and vascular endothelial cell mature markers in vitro. Furthermore, we identified that 24 proteins were down-regulated and 3 proteins were up-regulated in the 5(th) BM-MSCs in comparison to the 1(st) BM-MSCs, using mass spectrometry following two-dimensional electrophoresis. Our data suggest that transplantation of the 1(st) BM-MSCs may be an effective therapeutic strategy for cardiac tissue regeneration following AMI, and altered protein expression profiles between the 1(st) BM-MSCs and 5(th) passage BM-MSCs may account for the difference in their maintenance of stemness and their therapeutic effects following AMI.  相似文献   

16.
The need to provide rigid bony fixation in the surgical treatment of craniofacial deformities has inspired an on-going evolution of surgical innovations and implants. Because of the young age of many treated craniosynostosis patients and the unique pattern of cranial vault growth, the extensive implantation of metal devices is potentially problematic. The use of resorbable plate and screw devices offers all of the benefits of rigid fixation without many of their potential risks. Since the introduction of resorbable plate and screw devices in 1996, tens of thousands of craniofacial patients have received implants, but long-term results from a large series have yet to be reported. A combined prospective and retrospective analysis was done on 1883 craniosynostosis patients under 2 years of age treated by 12 surgeons from seven different geographic locations over a 5-year period who used the same type of resorbable bone fixation devices (poly-L-lacticpolyglycolic copolymer). Specifically, the incidence of postoperative infection, fixation device failure, occurrence of delayed foreign-body reactions, and the need for reoperation resulting from device-related problems were determined. Technical difficulties and trends in device use were also noted. From this series, significant infectious complications occurred in 0.2 percent, device instability primarily resulting from postoperative trauma occurred in 0.3 percent, and self-limiting local foreign-body reactions occurred in 0.7 percent of the treated patients. The overall reoperation rate attributable to identifiable device-related problems was 0.3 percent. Improved bony stability was gained by using the longest plate geometries/configurations possible and bone grafting any significant gaps across plated areas that were structurally important. The specific types of plates and screws used evolved over the study period from simple plates, meshes, and threaded screws to application-specific plates and threadless push screws whose use varied among the involved surgeons. This report documents the safety and long-term value of the use of resorbable (LactoSorb) plate and screw fixation in pediatric craniofacial surgery in the infant and young child. Device-related complications requiring reoperation occurred in less than 0.5 percent of the implanted patients, which is less frequent than is reported for metallic bone fixation. Resorbable bone fixation for the rapidly growing cranial vault has fewer potential complications than the traditional use of metal plates, screws, and wires.  相似文献   

17.
With a selected spectrum of coagulation tests the functioning capacity of thrombocytes was investigated in rabbits exposed to a whole body irradiation by means of 60Co radiation with a LD 5/30. A reduced retraction could be proved for times of irradiation (the 5th, 8th, 11th, 21st, 35th, and 56th day). A reduced formation of malondialdehyde could be identified in thrombocytes on the 8th and 21st day after irradiation. No changes could be found in determining adhesiveness, platelet aggregation caused by ADP, and PF3A and PF3F tests. In the course of additional investigations (coagulation time in unprepared and siliconized glass tubes, thromboelastogramme, activated partial chromboplastine time), significant changes of coagulation time could be observed in siliconized glass tubes on the 8th, 11th, 21st, and 56th day following irradiation.  相似文献   

18.
The study of the biological course of a vascularized osseous graft was performed on 64 fibulae in rabbits. Using radiography, standard histology, tetracyclines markage and study of 47-calcium incorporation as means of control. The time-limits of control are fixed at the 5th, 10th, 15th and 21st day and at the 1st, 2nd, 3rd and 5th month. The results show that if they are vascularized or not, the osseous grafts are not subjected to the rule: everything or nothing: "everything is not living in a vascularized osseous graft and everything is not dying in a conventional osseous graft". As for the good quality of the recipient bed, there is no significant difference between the healing time of those two types of grafts.  相似文献   

19.
Studies were carried out on the model of regeneration of mechanically removed elasmoid scales. Regenerating scales were morphologically analyzed using light and electron microscopy. It was found that the cells responsible for regeneration of the elasmoid scale plates could be classified as osteogenic elements. Little differentiated preosteoblasts were detected in the connective tissue of dermis on day 3 of regeneration, while partially calcified plates underlaid osteoblasts on day 7. The scale cover was fully restored on day 14 and it took two days for each bone plate to be formed. Osteocytes, fully differentiated osteogenic elements, were found in the deepest regions of newly formed scales.  相似文献   

20.
Studies were carried out on the model of regeneration of mechanically removed elasmoid scales. Regenerating scales were morphologically analyzed using light and electron microscopy. It was found that the cells responsible for regeneration of the elasmoid scale plates could be classified as osteogenic elements. Little differentiated preosteoblasts were detected in the connective tissue of dermis on day 3 of regeneration, while partially calcified plates underlay osteoblasts on day 7. The scale cover was fully restored on day 14 and it took two days for each bone plate to be formed. Osteocytes, fully differentiated osteogenic elements, were found in the deepest regions of newly formed scales.  相似文献   

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