Skeletal Bone Growth Research Articles

Weight and linear growth of the skeleton of domestic reindeer of the Nenets breed

Reindeer are one of the most widespread and adapted representatives of the northern territories of the Arctic zone of the Russian Federation. Features of skeletal development are an important ontogenetic feature that reflects the level of development of the animal and the degree of realization of its genetic resource in the phenotype. The purpose of the presented research is to study the characteristics of the growth and development of the skeleton of the Nenets reindeer breed, taking into account the sex and age of the animals. Data were obtained on the peripheral and axial growth of skeletal bones from birth to the end of growth of males and females. Based on the studies conducted, it was possible to establish that in the postnatal period, the axial part of the skeleton of male and female reindeer grows faster than the peripheral part. Linear bone growth in deer ends earlier than weight growth. Females, compared to males, are characterized by more intense weight and linear growth of the skeleton, which confirms the relatively earlier completion of the growth and development of the body of females in relation to males of the same age. The growth rate of the reindeer skeleton is inferior to the rate of increase in live weight, which increases mainly due to the active growth of other tissues and organs. The greatest increase in skeletal mass and linear growth is observed during the milk period. Consequently, the first six months of a reindeer’s life are of great importance for the formation of physique, physiological precocity and the level of future meat and labor productivity. The revealed patterns of skeletal growth for reindeer of the Nenets breed do not exclude the possibility of extending them to reindeer of other breeds.

Dynamics of the growth of exterior and interior indicators in ontogenesis in chickens of gene pool populations and broilers

Conformities of intensity of growth of muscles and bones of the skeleton in relation to the growth of body weight in chickens of the combined type of productivity and broilers have been studied . The research subject were chickens of meat and egg populations : experimental golden-striped (GS), Pushkinskaya from the bioresource collection of Russian Research Institute of Farm Animal Genetics and Breeding and broilers of the Ross 308 cross . The absolute values of body weight , muscle mass , length and thickness of skeletal bones in different age periods were calculated . Studies have shown that the mass of the pectoral and leg muscles has the highest growth rate in all the studied groups . The growth rate of the exterior and interior indicators decreases unevenly with age , especially in broiler chickens . The intensity of the growth of muscles and bones of the skeleton relative to the growth of body weight has been studied using an allometric equation . Studies have shown that the growth of the pectoral and leg muscles in all groups of chickens in the period up to 10 weeks of life outstrips the growth of the body as a whole . The growth of skeletal bones is characterized by negative allometry . Knowledge of the patterns of growth and development of the bird organism and its individual parts allows to adjust the feeding diet depending on the growth period , monitor the correctness of development and deviations from the standard , as well as choose the most informative periods for the selection of breeding birds .

Oleuropein and hydroxytyrosol protect rats’ pups against bisphenol A induced hypothyroidism

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats.

The role of particulate guanylyl cyclase B (GC-B) in auditory function in adult mice

Background cGMP signaling triggered by the binding of C-type natriuretic peptide (CNP) to its receptor guanylyl cyclase B (GC-B; NPR2; NPRB) has been linked by genetic evidence to a remarkable variety of physiological functions like skeletal bone growth, female fertility, cardiac growth, fat metabolism and gastrointestinal function. For the nervous system it has been recently demonstrated that the CNP/GC-B/cGMP/cGMP-dependent protein kinase type I (cGKI) signaling pathway is essential for sensory axon branching at the dorsal root entry zone of the spinal cord and at the rhombomeres of the hindbrain during embryonic development [1]. Also in the auditory system, distinct auditory nerve fiber (ANF) types that differ in their discharge rate and sound sensitivity bifurcate in the cochlear nucleus (CN), sending collaterals to the anteroventral, posteroventral, and dorsal subdivisions. The lack of GC-B has been shown to lead to a central phenotype [2].

Abstracts of the IBRA Conference on Surgery of the Head, 6th International Orthognathic Surgery Forum, February 14-15, 2014, Interlaken, Switzerland.

The multi-step treatment of severe dentofacial deformities starts after the termination of skeletal bone growth. In cases of additional transversal discrepancies the SARPE procedure has to be executed at first, followed by the orthodontic alignment of the dental arches. Then the at least three step treatment starts: it consists of the pre- and postoperative orthodontic treatment and the treatment in between surgical correction. This combined treatment may last up to three years and longer. For economic reasons as well as for an increasing motivation of the patient the ‘Surgery First’ concept was developed to reduce treatment time. We take advantage of the Regional Acceleration Procedure (RAP), which is known since Kole published the interdental corticotomy in the crowded lower front to accelerate the orthodontic alignment in the 1950s. Instead of hyrax screws for transversal widening we prefer he application of bone borne devices for SARPE procedures. Fixed appliances treatment starts earlier using RAP effect. Instead of preoperative orthodontic treatment we start with the operation and align the dental arches postoperatively within 6-8 months. Advantages of ‘Surgery First’: • The patient sees the operative results immediately. • Orthodontic treatment is accelerated by RAP effect. • Treatment is completed after 6-8 months, sometimes after 10 months. Disadvantages of ‘Surgery First’: • Orthodontists must be experienced and needs to plan the treatment in advance. • More close cooperation between surgeon and orthodontist is needed. • Orthodontic treatment starts 1-2 weeks after the operation with intervals of two weeks. • RAP effect takes three to four months. The ‘Surgery First’ concept can be performed easily with stable results in Angle Class II and III cases with crowding, frontal compensation and pronounced Spee curve. (Segmented) Bimaxillary osteotomies with or without CWR or CCWR can be performed with additional procedures as chin correction or jaw bone augmentation. The ‘Surgery First’ concept delivers safe results also in open bite cases, elongated front regions, minor transversal discrepancies and asymmetries. In cases of severe facial deformities and transversal discrepancies ‘Surgery First’ cannot be recommended yet.

Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival.

Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has clinical potential to treat fractures or to slow osteoarthritic progression by enhancing chondrocyte survival and slowing hypertrophy.

Extracellular matrix and developing growth plate.

Growth plate is a specialized cartilaginous structure that mediates the longitudinal growth of skeletal bones. It consists of ordered zones of chondrocytes that secrete an extracellular matrix (ECM) composed of specific types of collagens and proteoglycans. Several heritable human skeletal dysplasias are caused by mutations in these ECM components and this review focuses on the roles of type II, IX, X, and XI collagens, aggrecan, matrilins, perlecan, and cartilage oligomeric matrix protein in the growth plate as deduced from human disease phenotypes and mouse models. Substantial advances have been achieved in deciphering the interaction networks and individual roles of these components in the construction of the growth plate ECM. Furthermore, ER stress and other cellular responses have been identified as key downstream effects of the ECM mutations contributing to abnormal growth plate development. The next challenge is to utilize the molecular level knowledge for the development of potential therapeutics.

Activating transcription factor-2 affects skeletal growth by modulating pRb gene expression

Endochondral ossification is the process of skeletal bone growth via the formation of a cartilage template that subsequently undergoes mineralization to form trabecular bone. Genetic mutations affecting the proliferation or differentiation of chondrocytes result in skeletal abnormalities. Activating transcription factor-2 (ATF-2) modulates expression of cell cycle regulatory genes in chondrocytes, and mutation of ATF-2 results in a dwarfed phenotype. Here we investigate the regulatory role that ATF-2 plays in expression of the pocket proteins, cell cycle regulators important in cellular proliferation and differentiation. The spatial and temporal pattern of pocket protein expression was identified in wild type and mutant growth plates. Expression of retinoblastoma (pRb) mRNA and protein were decreased in ATF-2 mutant primary chondrocytes. pRb mRNA expression was coordinated with chondrogenic differentiation and cell cycle exit in ATDC5 cells. Type X collagen immunohistochemistry was performed to visualize a delay in differentiation in response to loss of ATF-2 signaling. Chondrocyte proliferation was also affected by loss of ATF-2. These studies suggest pRb plays a role in chondrocyte proliferation, differentiation and growth plate development by modulating cell cycle progression. ATF-2 regulates expression of pRb within the developing growth plate, contributing to the skeletal phenotype of ATF-2 mutant mice through the regulation of chondrocyte proliferation and differentiation.

Leptin is a potent stimulator of bone growth in ob/ob mice

Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. The lack of leptin in ob/ob mice, who are homozygous for the obese gene, results in hyperglycemia, hyperinsulinemia, hyperphagia, obesity, infertility, decreased brain size and decreased stature. To this end, we investigated the role of leptin as a hormonal regulator of bone growth. Leptin administration led to a significant increase in femoral length, total body bone area, bone mineral content and bone density in ob/ob mice as compared to vehicle treated controls. The increase in total body bone mass was a result of an increase in both trabecular and cortical bone mass. These results suggest that the decreased stature of the ob/ob mouse is due to a developmental defect that is readily reversible upon leptin administration. Our demonstration that the signalling or long form (Ob-Rb) of the leptin receptor is present in both primary adult osteoblasts and chondrocytes suggests that the growth promoting effects of leptin could be direct. In summary, these results indicate a novel role for leptin in skeletal bone growth and development.

Biosynthesis of rat growth plate proteoglycans in diabetes and malnutrition.

Insulin is an important growth factor in man and mammals. In the present investigation, we have studied the incorporation of (35S)-sulfate into growth plate proteoglycans in normal, diabetic, insulin-treated diabetic, and marasmic rats. We found that diabetes leads to an all-but-total stop in the synthesis of sulfated glycosaminoglycans. The glycosaminoglycan chains actually synthesized were shorter than in normal rats. The proteoglycan monomers were smaller and did not form large aggregates in vitro. Marasmic rats and insulin-treated diabetic rats were intermediate between normal and diabetic rats with respect to sulfate uptake by cartilage, incorporation of cartilage sulfate into glycosaminoglycans, and the chain length of glycosaminoglycans. We conclude that insulin and nutrition play important but different roles in the biosynthesis of growth plate proteoglycans and thus for the longitudinal growth of skeletal bones.