SEARCH · Search PubMed

Results for “Growth Plate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2006

Fibroblast growth factor expression in the postnatal growth plate.

Fibroblast growth factor (FGF) signaling is essential for endochondral bone formation. Mutations cause skeletal dysplasias including achondroplasia, the most common human skeletal dysplasia. Most previous work in this area has focused on embryonic chondrogenesis. To explore the role of FGF signaling in the postnatal growth plate, we quantitated expression of FGFs and FGF receptors (FGFRs) and examined both their spatial and temporal regulation. Toward this aim, rat proximal tibial growth plates and surrounding tissues were microdissected, and specific mRNAs were quantitated by real-time RT-PCR. To assess the FGF system without bias, we first screened for expression of all known FGFs and major FGFR isoforms. Perichondrium expressed FGFs 1, 2, 6, 7, 9, and 18 and, at lower levels, FGFs 21 and 22. Growth plate expressed FGFs 2, 7, 18, and 22. Perichondrial expression was generally greater than growth plate expression, supporting the concept that perichondrial FGFs regulate growth plate chondrogenesis. Nevertheless, FGFs synthesized by growth plate chondrocytes may be physiologically important because of their proximity to target receptors. In growth plate, we found expression of FGFRs 1, 2, and 3, primarily, but not exclusively, the c isoforms. FGFRs 1 and 3, thought to negatively regulate chondrogenesis, were expressed at greater levels and at later stages of chondrocyte differentiation, with FGFR1 upregulated in the hypertrophic zone and FGFR3 upregulated in both proliferative and hypertrophic zones. In contrast, FGFRs 2 and 4, putative positive regulators, were expressed at earlier stages of differentiation, with FGFR2 upregulated in the resting zone and FGFR4 in the resting and proliferative zones. FGFRL1, a presumed decoy receptor, was expressed in the resting zone. With increasing age and decreasing growth velocity, FGFR2 and 4 expression was downregulated in proliferative zone. Perichondrial FGF1, FGF7, FGF18, and FGF22 were upregulated. In summary, we have analyzed the expression of all known FGFs and FGFRs in the postnatal growth plate using a method that is quantitative and highly sensitive. This approach identified ligands and receptors not previously known to be expressed in growth plate and revealed a complex pattern of spatial regulation of FGFs and FGFRs in the different zones of the growth plate. We also found temporal changes in FGF and FGFR expression which may contribute to growth plate senescence and thus help determine the size of the adult skeleton.

Animals↗

PubMed2003

Systemic and local regulation of the growth plate.

The growth plate is the final target organ for longitudinal growth and results from chondrocyte proliferation and differentiation. During the first year of life, longitudinal growth rates are high, followed by a decade of modest longitudinal growth. The age at onset of puberty and the growth rate during the pubertal growth spurt (which occurs under the influence of estrogens and GH) contribute to sex difference in final height between boys and girls. At the end of puberty, growth plates fuse, thereby ceasing longitudinal growth. It has been recognized that receptors for many hormones such as estrogen, GH, and glucocorticoids are present in or on growth plate chondrocytes, suggesting that these hormones may influence processes in the growth plate directly. Moreover, many growth factors, i.e., IGF-I, Indian hedgehog, PTHrP, fibroblast growth factors, bone morphogenetic proteins, and vascular endothelial growth factor, are now considered as crucial regulators of chondrocyte proliferation and differentiation. In this review, we present an update on the present perception of growth plate function and the regulation of chondrocyte proliferation and differentiation by systemic and local regulators of which most are now related to human growth disorders.

Animals↗

PubMed2001

Glucocorticoids, thyroid hormone and growth hormone interactions: implications for the growth plate.

Linear growth occurs during childhood and results from endochondral ossification in the growth plate. Prepubertal growth is primarily regulated by growth hormone (GH) and insulin-like growth factor (IGF)-I, with important contributions from glucocorticoids (GC) and thyroid hormone (T(3)). The somatomedin hypothesis proposed that GH stimulates hepatic IGF-I production, which then regulates growth via IGF-I receptor expressing chondrocytes in an endocrine fashion. Recent studies indicate that locally acting IGF-I is a key determinant of endochondral ossification and that GH, GC and T(3) regulate expression of IGF-I and its receptor in the growth plate directly. Analysis of hormone imbalance during childhood and studies of genetically modified mice provide support for an important GH and IGF-I autocrine/paracrine pathway and for direct effects of GC and T(3) during endochondral ossification. Thus, the epiphyseal growth plate is a key site for convergent hormone action that mediates the control of linear growth.

Animals↗

PubMed1990

Growth-plate chondrocyte cultures for reimplantation into growth-plate defects in sheep. Characterization of cultures.

Damage to epiphyseal growth plates due to fracture, trauma, or infection can lead to invasion of bone across the cartilage and localized arrest of long-bone growth. The implantation of a viable de novo cartilage plug into such defects may provide the appropriate cartilage presence necessary to inhibit the initial formation of bony bridges across the epiphysis and so maintain the growth potential. De novo cartilage plugs were prepared from ovine growth plates by culturing isolated epiphyseal chondrocytes from fetal lambs. After 14 days of culture, these de novo cartilage discs were composed of chondroitin sulfate, a small amount (5%) of dermatan sulfate, and cartilage-specific collagen. The cellular morphology and the histochemistry resembled resting zones of normal growth-plate cartilage. Those de novo cartilage discs, which had been embedded in gelled Type I collagen, retained their morphology and could be easily manipulated. On the other hand, Type II collagen and a polyuronic acid gauze (Surgicel) were not satisfactory substrates to facilitate subsequent transplantation into growth-plate defects. The use of 5-carboxyfluorescein diacetate succinimidyl ester (CSFE) throughout the cultures of epiphyseal chondrocytes or prolonged incorporation of [3H]-thymidine appeared to label the cells with useful markers for following their fate subsequent to implantation in vivo.

Animals↗

PubMed2004

Primary culture of rat growth plate chondrocytes: an in vitro model of growth plate histotype, matrix vesicle biogenesis and mineralization.

During endochondral ossification (EO), cartilage is replaced by bone. Chondrocytes of growth plate undergo proliferation, maturation, hypertrophy, matrix vesicle (MV) biogenesis and programmed cell death (PCD, apoptosis). The in vitro system presented here provides a potential experimental model for studying in vitro differentiation and MV biogenesis in chondrocyte cultures. Chondrocytes were obtained from collagenase-digested tibial and femoral growth plate cartilage of 7-week-old rachitic rats. The isolated chondrocytes were plated as monolayers at a density of 0.5 x 10(6) cells per 35-mm plate and grown for 17 days in BGJ(b) medium supplemented with 10% fetal bovine serum, 50 microg/ml ascorbic acid. Light microscopy revealed Sirius red-positive, apparent bone matrix in layers at the surfaces of cartilaginous nodules that developed in the cultures. The central matrix was largely alcian blue staining thus resembling cartilage matrix. Electron microscopy revealed superficial areas of bone like matrix with large banded collagen fibrils, consistent with type I collagen. Most of the central matrix was cartilaginous, with small fibrils, randomly arranged consistent with type II collagen. The presence of peripheral type I and central type II and type X collagen was confirmed by immunohistochemical staining. Immunohistochemistry with anti-Bone morphogenetic proteins 2, 4 and 6 showed that BMP expression is associated with maturing hypertrophic central chondrocytes, many of which were TUNEL positive and undergoing cell death with plasma membrane breaks, hydropic swelling and cell fragmentation. During early mineralization, small radial clusters of hydroxyapatite-like mineral were associated with matrix vesicles. Collagenase digestion-released MVs from the cultures showed a high specific activity for alkaline phosphatase and demonstrated a pattern of AMP-stimulated nonradioactive (40)Calcium deposition comparable to that observed with native MVs. These studies confirm that primary cultures of rat growth plate chondrocytes are a reasonable in vitro model of growth plate histotype, MV biogenesis and programmed cell death.

Alkaline Phosphatase↗

PubMed1998

[The assessment of changes of the plate growth in Blount disease by MRI].

The changes within growth plates around the knee in Blount disease have been analyzed with MRI in 4 patients with late onset tibia vara. Extensive changes were found in both tibial and femoral growth plate. General widening of the plate, invagination into metaphysis and high intensity irregularities of the shape were observed. Lateral aspect of both physes was involved to higher degree. Our study supports mechanical etiology of the late onset tibia vara. In our opinion long lasting distraction stress on the lateral aspect of the knee due to the varus deformity might be responsible for the changes observed in MRI.

Adolescent↗

PubMed2004

Zone-specific micromechanical properties of the extracellular matrices of growth plate cartilage.

Growth plate cartilage demonstrates a unique capacity for cell proliferation and matrix synthesis while sustaining mechanical stresses. To test the hypothesis that the extracellular matrices along various depth of growth plate cartilage have different elastic properties, microindentation by atomic force microscopy was applied to en bloc dissected rabbit cranial base growth plate samples from the reserve zone to mineralizing zone in 50-microm increments. The average elastic modulus upon transverse indentation orthogonal to the long axis of the growth plate showed a gradient distribution, increasing significantly from the reserve zone (0.57 +/- 0.05 MPa) to mineralizing zone (1.41 +/- 0.19 MPa). Longitudinal indentation of the reserve zone along the long axis of the growth plate revealed an average elastic modulus of 0.77 +/- 0.12 MPa, significantly different from the same zone upon transverse indentation. Thus, the extracellular matrix of growth plate cartilage seems to be inhomogenous in its capacity to withstand mechanical stresses.

Animals↗

PubMed1986

Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate.

Whether growth hormone stimulates longitudinal bone growth by a direct effect at the site of the growth plate or indirectly by increasing the concentration of circulating somatomedins (insulin-like growth factors) has been the subject of controversy. Immunohistochemical methods were used to explore the localization and distribution of insulin-like growth factor I (IGF-I) immunoreactivity in the epiphyseal growth plate of the proximal tibia of male rats. Cells in the proliferative zone of the growth plate of normal rats exhibited a bright immunofluorescence, whereas cells in the germinal and hypertrophic zones stained only weakly. In rats subjected to hypophysectomy, the number of fluorescent cells was markedly reduced. When the hypophysectomized rats were treated with growth hormone, either systemically or at the site of the growth plate, the number of IGF-I-immunoreactive cells in the proliferative zone was increased. The results show that IGF-I is produced in proliferative chondrocytes in the growth plate and that the number of IGF-I-containing cells is directly regulated by growth hormone. These findings suggest that IGF-I has a specific role in the clonal expansion of differentiated chondrocytes and exerts its function locally through autocrine or paracrine mechanisms.

Animals↗

PubMed2003

Physiology and pathophysiology of the growth plate.

Longitudinal growth of the skeleton is a result of endochondral ossification that occurs at the growth plate. Through a sequential process of cell proliferation, extracellular matrix synthesis, cellular hypertrophy, matrix mineralization, vascular invasion, and eventually apoptosis, the cartilage model is continually replaced by bone as length increases. The regulation of longitudinal growth at the growth plate occurs generally through the intimate interaction of circulating systemic hormones and locally produced peptide growth factors, the net result of which is to trigger changes in gene expression by growth plate chondrocytes. This review highlights recent advances in genetics and cell biology that are illuminating the important regulatory mechanisms governing the structure and biology of the growth plate, and provides selected examples of how studies of human mutations have yielded a wealth of new knowledge regarding the normal biology and pathophysiology of growth plate cartilage.

Animals↗

PubMed1992

Spaceflight and age affect tibial epiphyseal growth plate histomorphometry.

Growth plate histomorphometry of rats flown aboard the Soviet biosatellite COSMOS 2044, a 14-day spaceflight, was compared with that of control groups. In growth plates of flight animals, there was a significant increase in cell number per column and height of the proliferative zone and a reduction in height and cell number in the hypertrophy/calcification zone. No significant differences were found in matrix organization at the ultrastructural level of flight animals, indicating that although spaceflight continues to affect bone growth of 15-wk-old rats, extracellular matrix is not altered in the same manner as seen previously in younger animals. All groups showed growth plate characteristics attributed to aging: lack of calcification zone, reduced hypertrophy zone, and unraveling of collagen fibrils. Tail-suspended controls did not differ from other controls in any of the parameters measured. Our results suggest that growth plates of older rats are less responsive to unloading by spaceflight or suspension than those of younger rats and provide new evidence about the modifying effect of spaceflight on the growth plate.

Aging↗

PubMedDate not supplied

Disseminated thrombosis-induced growth plate necrosis in rat: a unique model for growth plate arrest.

Exposure of rats to 2-butoxyethanol (BE) produces early hemolytic anemia and disseminated thrombosis. This leads to infarctions in multiple organs, including bones and cartilage. BE, administered for different durations of exposure in two separate experiments, produced metaphyseal vascular thrombosis, growth plate infarction, and partial or complete physeal growth arrest. This reproducible model may serve as a useful tool in the study of some conditions that manifest growth plate damage. The suitability of this model for investigating the pathogenesis of growth plate necrosis and as a model for potential therapy for various human growth plate disorders are discussed.

Animals↗

PubMed1993

Growth hormone receptors in avian epiphyseal growth-plate chondrocytes.

Growth hormone receptor (GH-R) gene expression was evaluated in avian growth-plate cartilage by Northern blot and hybridization using the avian GH-R probe. A single transcript of approximately 5.2 kb was demonstrated in cultured growth-plate chondrocytes as well as in growth-plate extracts. GH receptor gene expression was inhibited by chicken GH (cGH) in a dose- and time-dependent manner. Chicken GH was more potent in down-regulating the GH-R gene expression than hGH, but on the other hand cGH exhibited a lower affinity to avian chondrocytes receptor than did the human hormone. Addition of ascorbic acid to the culture media caused cell differentiation: induction of alkaline phosphatase activity and attenuation of collagen type II gene expression. No differences in the GH-R gene expression were observed in the nondifferentiated cells compared with the differentiated cells. Chicken GH did not form any complex with the purified hGH binding protein (hGHBP), did not bind to human lymphocytes GH receptor, and did not affect Nb2 cell proliferation. These systems represent somatogenic and lactogenic types of GH receptors, respectively. In summary, avian growth-plate chondrocytes in situ and in culture exhibit GH-R and these receptors are capable of binding GH. Thus, the failure of GH to affect avian chondrocytes' proliferation was not due to either the absence of receptors on the cell membrane or to a lack in its binding activity, but rather may be due to events farther downstream.

Alkaline Phosphatase↗

PubMed1991

Computer simulations of chondrocytic clone behaviour in rabbit growth plates.

The growth behaviour of chondrocytic clones in the cell columns of the proximal tibial growth plates of young rabbits was modelled in computer simulations. Simulations were performed, modelling either clones in large groups of columns or clones in one single column. The former were based on morphological data and measurements of cell columns from an earlier study while the latter utilised previous findings of cellular kinetics in rabbit growth plates. Simulation results that resembled most closely the actual observations on rabbit growth plates were those in which a distribution of values was assumed both for clone length (ranging from 1000 to 2000 microns) and for the lengths of the discontinuities between clones. When the assumption was made in the models that the disappearing (metaphyseal) end of an 'old' clone moved more rapidly than the developing (epiphyseal) end of a 'new' clone, replacing the former, the length of the discontinuity between these two clones increased with time. This assumption, which could be modelled in the simulations of clones in a single column based on cell growth behaviour, was found to provide an explanation for an earlier finding that there are more short columns at the epiphyseal side than at the metaphyseal side of a growth plate.

Animals↗

PubMedDate not supplied

Muscle-based gene therapy and tissue engineering for treatment of growth plate injuries.

Growth plate injuries may lead to a progressive angular deformity or longitudinal growth disturbance. The authors investigated the feasibility of gene therapy and tissue engineering based on autologous muscle-and adenoviral-mediated gene transfer of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) to treat tibial physeal defects in rabbits. The medial half of the left proximal tibial growth plate was completely excised in 44 6-week-old New Zealand white rabbits. Four experimental groups were created: no treatment (I), autologous muscle interposition (II), autologous muscle interposition injected with adIGF-1 (III), and autologous muscle interposition injected with adBMP-2 (IV). Radiographic and histologic assessments were obtained postoperatively. Significant tibial shortening and a compact osseous bridge were observed in groups I and IV. Growth plates remained open in groups II and III. This experiment demonstrates that IGF-1 had a supportive effect on physeal chondrocytes, while BMP-2 caused increased osteogenic activity in the injured growth plates.

Adenoviridae↗

PubMed2006

Roles of COX-2 and iNOS in the bony repair of the injured growth plate cartilage.

Growth plate injuries often lead to bone growth defects, which primarily occur due to bony repair at injury sites. Bony repair is preceded by an injury-induced inflammatory response, which could play a role in regulating the repair process. Here, roles of two inflammatory mediators, cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), in the injury responses were analysed by examining their gene expression and effects of blocking their activities, respectively, with celecoxib and aminoguanidine during 2 days prior to and until 7 days after injury in a rat tibial growth plate injury model. Quantitative RT-PCR assays revealed upregulated expression of COX-2 on days 1 and 4 and iNOS on day 1. Histological analysis of injury sites revealed significant reductions in inflammatory infiltrate (particularly neutrophils) on day 1 in treated groups compared to saline control. While bony tissue proportions at injury sites were unaffected by either treatment, mesenchymal tissue proportions were larger but cartilaginous tissue proportions were smaller on day 8 (though statistically insignificant), and bone remodelling appeared delayed with a smaller bone marrow proportion on day 14 in both treatment groups. These findings suggest that COX-2 and iNOS mediate injury-induced inflammatory response, and may play a role in enhancing mesenchymal cell differentiation to cartilaginous cells and in promoting bone remodelling during bony repair of growth plate injury sites. Furthermore, increased expression of cartilage-related (collagen-2, collagen-10, SOX-9) and bone-related molecules (osteocalcin, cbfalpha-1) suggest involvement of both endochondral and direct bone formation mechanisms during bony repair.

Animals↗

PubMed1987

The normal and abnormal growth plate.

Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities.

Bone Diseases↗

PubMed2006

Elevated expression of hypoxia inducible factor-2alpha in terminally differentiating growth plate chondrocytes.

Growth plate chondrocytes exist in a hypoxic environment where it is recognized that hypoxia-inducible factor-1alpha (HIF-1alpha) is essential for their survival. Its regulation of chondrocyte viability may be mediated by the increased expression of vascular endothelial growth factor (VEGF) and glycolytic enzymes. However, the full chondrocyte response to hypoxia and the molecular control of VEGF expression in relation to growth plate differentiation and vascularization remains poorly understood. Using Percoll density gradient centrifugation, chick chondrocytes were separated into populations of different maturational phenotype. A differential display analysis of the populations showed highly upregulated expression of HIF-2alpha mRNA during chondrocyte differentiation. HIF-2alpha is a homologue of the HIF-1alpha transcription factor, both of which play a role in the activation of a number of hypoxia responsive genes. HIF-1alpha mRNA was also found to be expressed, although levels of expression were found to be similar in all of the chondrocyte fractions. The elevated expression of HIF-2alpha during chondrocyte differentiation was accompanied by increased VEGF expression. Analysis of the murine chondrocyte cell line, ATDC5, which undergoes ordered maturation indicated that HIF-2alpha, VEGF, placental growth factor, and glucose transporter-1 expression all increased in parallel with chondrocyte differentiation. This observation was supported by immunohistochemistry on sections of mouse bone which showed staining corresponding to the presence of HIF-2alpha in hypertrophic growth plate chondrocytes. The presence of HIF-2alpha was also observed in articular chondrocytes but was restricted to the superficial tangential zone. HIF-2alpha is, therefore, likely to be involved in the initiation of blood vessel formation and a metabolic shift in the growth plate, processes crucial for endochondral ossification.

Animals↗

PubMed1988

Increased cAMP production after short-term capacitively coupled stimulation in bovine growth plate chondrocytes.

Growth plate chondrocytes from newborn calf costochondral junctions grown in monolayer were subjected to a capacitive AC signal of 500 V peak to peak (P-P) at 60 kHz for 48 h and were analyzed for [3H]thymidine uptake. The stimulated chondrocytes showed a 130% greater uptake over unstimulated controls. Other newborn calf growth plate chondrocytes were stimulated at 500 V P-P at 60 kHz for 2.5, 5.0, 10.0, and 20.0 min and were analyzed for cAMP. Chondrocytes stimulated for 2.5 and 5.0 min showed a 142.8% (p less than 0.05) and 394.5% (p less than 0.01) increase over controls, respectively. The chondrocytes stimulated for 10.0 and 20.0 min showed no significant difference from the controls. It is concluded that short-term exposure of growth plate chondrocytes to an appropriate capacitively coupled field stimulates cAMP production, but longer-term application of the electrical field is ineffective.

Animals↗