Cell kinetics and longitudinal bone growth in birds

The theory that links cell division in epiphyseal cartilage plates to overall growth of long bones has been extended from linear growth systems to those in which proliferating and hypertrophied cells are not arranged in columns. Consideration has also been given to the analysis of non-parallel growth systems. The theory is illustrated by examples from the growth of chicken bones.     

Delivering on the promise of bone morphogenetic proteins.

The advent of bone growth factors has been widely anticipated since their successful production using recombinant DNA technology. Bone morphogenetic proteins (BMPs) are an important class of bone growth factors and will be the focus of this article. In the near future these therapeutics might revolutionize how clinicians treat such diverse orthopedic applications as the healing of broken bones, increasing bone density lost through aging, and strengthening the spine. These potent proteins require application directly at the site of repair via a delivery system. The choice of delivery system has a profound effect on the clinical outcome. In the past decade, researchers have focused on developing efficient delivery systems and advancing these factors from the bench to the clinic.     

Osteohistological insight into the early stages of growth in Mussaurus patagonicus (Dinosauria,Sauropodomorpha)

Here, we describe the bone histology of juvenile specimens of the basal sauropodomorph Mussaurus patagonicus and interpret its significance in terms of the early growth dynamics of this taxon. Thin sections from three juvenile specimens (femur length, 111–120 mm) of Mussaurus were analysed. The sampled bones consist of multiple postcranial elements collected from the Late Triassic Laguna Colorada Formation (El Tranquilo Group, Patagonia). The cortical bone is composed of fibrolamellar bone tissue. Vascularisation is commonly laminar or plexiform in the long bones. Growth marks are absent in all the examined samples. The ‘epiphyses’ of long bones are all formed by well-developed hypertrophied calcified cartilage. The predominance of woven-fibred bone matrix in cortical bones indicates a fast growth rate in the individuals examined. Moreover, given the existence of growth marks in adult specimens of Mussaurus, as in other sauropodomorphs, and assuming that the first lines of arrested growth was formed during the first year of life, the absence of growth marks in all the bones suggest that the specimens died before reaching their first year of life. Compared with the African taxon Massospondylus carinatus (another basal sauropodomorph for which the bone histology has been previously studied), it appears that Mussaurus had a higher early growth rate than Massospondylus.     

Chondrocyte apoptosis enhanced at the growth plate: a physeal response to a diaphyseal fracture

Post-traumatic overgrowth of growing long bones is a common clinical phenomenon in paediatric traumatology and is the result of an enhanced stimulation of the nearby growth plate after fracture. To date, the exact post-fractural reactions of the growth plate are poorly understood. The aim of this study has been to determine the impact of fracture on the frequency of chondrocyte apoptosis of the growth plate. Rats sustained a mid-diaphyseal closed fracture of the left tibia or were left untreated. All animals were killed 3, 10, 14 or 29 days after trauma. The left and right tibiae were harvested and apoptotic chondrocytes of the proximal tibial growth plate were detected by TUNEL staining. The apoptosis percentage of physeal chondrocytes was statistically compared among fractured bones, intact contra-lateral bones and control bones. The physeal apoptosis rate of the fractured bone was significantly higher than that of the contra-lateral intact bone (valid for all evaluated days) and the control bone (valid from day 10 onwards). Contra-lateral intact tibiae never showed significantly higher apoptosis rates compared with control tibiae. Thus, mid-diaphyseal fracture influences the nearby growth plate by stimulating chondrocyte programmed cell death, which is associated with cartilage resorption and bone replacement. The lack of a significant difference between the intact contra-lateral and the intact control bone suggests that fracture only has a local effect that contributes to the greater apoptosis rate of the adjacent physis.     

The growth of the freshwater murrel,Ophicephalus punctatus Bloch

Summary The growth of O. punctatus has been studied from the zones on the opercular bones and scales. Size estimates obtained from the opercular bones and scales were further substantiated by length frequency distribution and back-calculations. A close agreement in length-age relationship was obtained by various methods. These observations provide adequate evidence towards the validity of age determination in O. punctatus.Growth rate differs markedly in the two sexes. Males grow faster than the females. To study the changes in length with age, von Bertalanffy growth equation and Gompertz curve were used. The theoretical lengths obtained from the von Bertalanffy equation agreed very closely with the observed lengths.There is sexual difference in the weight-length relationship of O. punctatus. Modal weight of each year class obtained according to age reading showed that growth in weight is faster in males. The theoretical growth equation gives a good fit for weight-age data. O. punctatus is generally a fish of the impounded waters. The interrelationship between pond environment and growth characteristics has been discussed.     

Natural markers in bone growth

Three features in the long bones, shown by radiograms, have been used as markers for the study of bone growth.

• (I) Transverse lines of arrested growth. Radiograms of six long limb bones from 1,576 individuals were investigated for clearness and persistence of these lines. Both ends of tibia and fibula showed very high frequency of suitable lines for markers, possibly also the distal end of femur and radius.
• (II) Notches in the base of second and fifth metacarpal bones. Measurements of growth from apex of the basal notch to the ends of the shaft were performed on serial hand radiograms. The proportion of growth from distal and basal ends averaged 87:13 in the second and 80:20 in the fifth metacarpal bones.
• (III) Nutrient canals. The initial point of ossification was determined by a prolongation of the nutrient canal intersecting the central axis of the medullary cavity. The proportion of growth from that point to distal and basal ends of the shaft averaged 68:32 and 64:36 for the second and the fifth metacarpal bones, respectively. These values are significantly different from the measurements obtained from the notches.

     

Osteohistological analyses reveal diverse strategies of theropod dinosaur body-size evolution

The independent evolution of gigantism among dinosaurs has been a topic of long-standing interest, but it remains unclear if gigantic theropods, the largest bipeds in the fossil record, all achieved massive sizes in the same manner, or through different strategies. We perform multi-element histological analyses on a phylogenetically broad dataset sampled from eight theropod families, with a focus on gigantic tyrannosaurids and carcharodontosaurids, to reconstruct the growth strategies of these lineages and test if particular bones consistently preserve the most complete growth record. We find that in skeletally mature gigantic theropods, weight-bearing bones consistently preserve extensive growth records, whereas non-weight-bearing bones are remodelled and less useful for growth reconstruction, contrary to the pattern observed in smaller theropods and some other dinosaur clades. We find a heterochronic pattern of growth fitting an acceleration model in tyrannosaurids, with allosauroid carcharodontosaurids better fitting a model of hypermorphosis. These divergent growth patterns appear phylogenetically constrained, representing extreme versions of the growth patterns present in smaller coelurosaurs and allosauroids, respectively. This provides the first evidence of a lack of strong mechanistic or physiological constraints on size evolution in the largest bipeds in the fossil record and evidence of one of the longest-living individual dinosaurs ever documented.     

四川自贡大山铺中侏罗世蜀龙和峨眉龙长骨骨组织结构的初步研究

通过对四川自贡大山铺恐龙动物群中两种主要蜥脚类恐龙—李氏蜀龙和天府峨眉龙肱骨和尺骨的骨组织结构观察,并与我国晚白垩世的几种恐龙长骨进行对比,结果发现:1)恐龙的长骨都具有快速的后生生长速率;2)恐龙的生长方式属于非限定生长,即在成年后并不停止生长;3)不同类型的恐龙到了成年以后,其骨沉积速率可能有较大差异;4)不同类型的恐龙在长骨的生长改建过程中,骨组织内部的重吸收作用有较大差异;5)生长轮结构在不同部位的骨骼中或在骨骼的生长发育过程中可能也有较大差异。     

TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression

The development of endochondral bones requires the coordination of signals from several cell types within the cartilage rudiment. A signaling cascade involving Indian hedgehog (Ihh) and parathyroid hormone related peptide (PTHrP) has been described in which hypertrophic differentiation is limited by a signal secreted from chondrocytes as they become committed to hypertrophy. In this negative-feedback loop, Ihh inhibits hypertrophic differentiation by regulating the expression of Pthrp, which in turn acts directly on chondrocytes in the growth plate that express the PTH/PTHrP receptor. Previously, we have shown that PTHrP also acts downstream of transforming growth factor beta (TGFbeta) in a common signaling cascade to regulate hypertrophic differentiation in embryonic mouse metatarsal organ cultures. As members of the TGFbeta superfamily have been shown to mediate the effects of Hedgehog in several developmental systems, we proposed a model where TGFbeta acts downstream of Ihh and upstream of PTHrP in a cascade of signals that regulate hypertrophic differentiation in the growth plate. This report tests the hypothesis that TGFbeta signaling is required for the effects of Hedgehog on hypertrophic differentiation and expression of PTHRP: We show that Sonic hedgehog (Shh), a functional substitute for Ihh, stimulates expression of Tgfb2 and Tgfb3 mRNA in the perichondrium of embryonic mouse metatarsal bones grown in organ cultures and that TGFbeta signaling in the perichondrium is required for inhibition of differentiation and regulation of Pthrp expression by Shh. The effects of Shh are specifically dependent on TGFbeta2, as cultures from Tgfb3-null embryos respond to Shh but cultures from Tgfb2-null embryos do not. Taken together, these data suggest that TGFbeta2 acts as a signal relay between Ihh and PTHrP in the regulation of cartilage hypertrophic differentiation.     

Tubular hand bone growth during the latter half of the prenatal period: an allometric analysis

The growth of the 19 tubular hand bones from fetal months 5 to 9 was studied by the allometric method. The hand bones were carefully dissected under a low power stereoscopic microscope. The length and breadth of all bones was found to be monophasic in relation to crown-rump length. In general, maximum bone and ossified shaft lengths in the same row group demonstrate similar allometric coefficients. The specific growth rate of ossified shaft length for all fetal hand bones is greater than the growth rate of maximum length. The highest allometric coefficients for both maximum length and ossified shaft length were obtained from the middle phalanges. The shape of the metacarpals and distal phalanges becomes thinner, while the other bones become thicker or maintain their length-breadth ratio. The relative growth pattern of the first proximal phalanx differed from the middle phalangeal group of the other digits. This suggests that current nomenclatures for the three bones of the pollex is appropriate.     

An experimental study of craniofacial growth in a heterotopic rat head transplant

In order to examine whether or not facial bones are themselves able to regulate their own growth, we devised a new experimental model in which we transplanted the whole head of an infant rat to the body of an isohistogeneic adult rat by means of microvascular anastomoses. The advantage of this model is that the transplanted head has neither scars nor any moving soft tissues that could modify growth around facial bones. Using this model, we conducted a study of the nasomaxillary region that has led us to conclude that facial bones do in fact regulate their own growth. The results also suggested that facial bone sutures play a more active role in the growth process than presently suspected.     

Growth in revascularized bone grafts in young puppies.

The results of microvascular transfers of growing ulnas in puppy forelegs have been studied. These transfers were carried out both heterotopically and orthotopically. The growth in the revascularized bone grafts has been compared to that in heterotopic, nonvascularized ulna transfers and to normal ulnar growth. The growth in the vascularized bone grafts was significantly greater than in the nonvascularized grafts, but significantly less than in normal ulnar growth. A metaphyseal contribution to the blood supply of the growing portion of long bones is suggested.     

Antioxidant defense and aging in C. elegans: Is the oxidative damage theory of aging wrong?

The oxidative damage theory of aging once seemed almost proven. Yet recently the buzzards have been assembling in the blue skies above it. New challenges to the theory from work using nematode worms seem set to bring them down to peck at its bones. But is the theory really dead, or does it just need to be modified?     

Incidence of healed fracture in the skeletons of birds, molluscs and primates

The incidences of healed fracture in the limb bones of birds and the shells of molluscs were estimated by the examination of samples of bones and shells. The results are compared to published data on fracture incidence in molluscs and in primates and other mammals. The relationship between observed incidence of healed fracture, costs of growth and use of the skeleton, and the costs associated with its failure are discussed in terms of a theory of factors of safety.     

Strain patterns in the horncores, cranial bones and sutures of goats (Capra hircus) during impact loading

The design of bovid horns and skulls for the function of head-to-head fighting has been well studied using mechanical and kinematic analyses, but actual strain measurements from the horncores, cranium and sutures during impact loading have never been made. During in vitro impact loading of one or both horns on the heads of female domestic goats, principal strains were measured from the surfaces of the horncore bases, frontal and parietal bones, and interfrontal and frontoparietal sutures. Impact produced a bending moment at the bases of the horncores, with compressive strains on the posterior surfaces more than doubling the anterior tensile strains. These ratios of compression to tension exceed our predictions (and those in the literature) based on curved beam theory. Principal strains in the cranial bones dropped by as much as 50% crossing the sutures, which acted like springs or hinges to allow cranial bone movement. Sutures also experienced very high strain magnitudes, being more than 10 times greater than those of the surrounding cranial bones. Sutural strains during impact loading of the horns also greatly exceeded the strain levels recorded during mastication in other studies. The decrease in strain between adjacent cranial bones across a suture and the large strains at the sutures indicate that the sutures function as shock absorbers during impact.     

Principal component analysis of the elongation of metacarpal and phalangeal bones

A hypothesis that the first principal component computed from the covariance matrix of logarithms reflected the specific growth rates of corresponding bones was taken to analyze the growth pattern of the tubular bones of the hand. The total length of 19 tubular bones of the right hand was measured on standardized radiographs of Japanese children (33 boys, 33 girls). Metacarpals in boys and bones of the fifth digit in girls showed higher growth coefficients. The second, third and fourth proximal, and the third and fourth middle phalanges showed lower coefficients for both sexes. These observations suggest the signs of proximal row dominance in boys and of fifth ray dominance in girls in the elongation of the hand bones. A marked sex difference was found in the fifth middle phalanx. In girls the growth coefficients of this bone was much larger than any other bones, but was moderate in boys.     

PDGFBB promotes PDGFRα-positive cell migration into artificial bone in vivo

Bone defects caused by traumatic bone loss or tumor dissection are now treated with auto- or allo-bone graft, and also occasionally by artificial bone transplantation, particularly in the case of large bone defects. However, artificial bones often exhibit poor affinity to host bones followed by bony union failure. Thus therapies combining artificial bones with growth factors have been sought. Here we report that platelet derived growth factor bb (PDGFBB) promotes a significant increase in migration of PDGF receptor α (PDGFRα)-positive mesenchymal stem cells/pre-osteoblastic cells into artificial bone in vivo. Growth factors such as transforming growth factor beta (TGFβ) and hepatocyte growth factor (HGF) reportedly inhibit osteoblast differentiation; however, PDGFBB did not exhibit such inhibitory effects and in fact stimulated osteoblast differentiation in vitro, suggesting that combining artificial bones with PDGFBB treatment could promote host cell migration into artificial bones without inhibiting osteoblastogenesis.     

Morphofunctional changes in the long tubular bones of animals which have developed while readapting after physical loads

The investigation has been performed on 120 white male rats of Wistar line. By means of the morphometry, electron microscopy and chemical methods dynamics of readaptive changes have been studied in long tubular bones during the period, when the effect of physical loadings both of dynamic and static character and of various intensity has been stopped, up to the old periods of the animals' life. Readaptation after moderate dynamic and static loadings is occurring for a long time and steadily. The changes caused by static loadings are nearly completely restored in a year. Morphofunctional rearrangements of the long tubular bones in the readaptation process after moderate dynamic loadings is characterized by residual manifestations. Prolonged readaptation after intensive physical loadings does not result in a complete restoration of all the parameters studied concerning growth and skeletal development. An intensive dynamic loading produces more stable changes, that are not subjected to a complete correction even after a passive readaptation for a year. Readaptation morphofunctional rearrangements of the long tubular skeletal bones depend on conditions of the previous regimen of the motor activity.     

笼养白腹锦鸡幼鸟骨骼系统生长的研究

本文研究了笼养白腹锦鸡幼鸟从孵出之日起至143日龄的骨骼系统生长发育情况,并对部分骨骼的生长曲线进行了拟合。探讨了白腹锦鸡幼鸟生长模式对提高幼鸟成活率的意义。     

Kinematics of cranial vault growth in rabbits

To characterize mathematically the spatial rearrangement of cranial vault bones of the rabbit during growth, a longitudinal study was undertaken from age 4-20 weeks. Initially, at least three nonlinear tantalum bone markers were implanted in the parietal, frontal, and the combined nasal bones. Thereafter, the animals were followed regularly with roentgen stereophotogrammetrical analysis. The parietal bones were found to rotate laterally upward (3 degrees), while the frontal bones rotated downward (2 degrees) relative to their contralaterals. The frontal bones rotated rostrally upward (12 degrees) and outward (3 degrees) as well as laterally downward (5 degrees) in relation to the parietal bones. Due to the morphology of the rabbit head, the examination positioning used in this study, and the direction of the growth process, growth at the coronal suture correlated fairly well with longitudinal axis translations; but the growth at the frontonasal suture relative to the frontal bones was directed about 45 degrees downward. This points to the importance of the bone-marker positioning, so that their connecting line is directed along the axis of growth. Also, this approach makes it possible to obtain new information on the development and treatment of craniofacial aberrations.