Search PubMed⌕ Search

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.

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

At least 73 records · Page 4Linked to original sources
PubMed2002

The effects of dynamic axial loading on the rat growth plate.

Longitudinal bone growth can be suppressed by compressive loading. In this study, we applied three different magnitudes (17, 8.5, and 4N) of compressive force to growing rat ulnas 10 minutes/day for 8 days and investigated the effects on the distal growth plate biology. Further, to investigate growth rate recovery after cessation of loading, we examined rats 7 days after the loading period. Longitudinal growth of the ulna was suppressed in a dose-dependent manner by applied compressive force. In the 17N group, the longitudinal mineralization rate (LMR) at the distal growth plate was suppressed completely by loading and did not recover. However, in the 8.5N and 4N groups, LMR suppression recovered in 1 week. In the 17N group, growth plate height and hypertrophic zone height were significantly greater than control; the number of hypertrophic chondrocytes was increased; and some traumatic changes such as cracks in the growth plate were found. In addition, 17N loading suppressed cartilage mineralization and capillary invasion beneath the growth plate, although the number of chondrocytes synthesizing vascular endothelial growth factor (VEGF) was increased. Our study shows longitudinal growth suppression caused by axial loading of the ulna, which is proportional to the magnitude of load. Only the largest load (17N) caused morphological changes in the distal growth plate cartilage. There was no association found between mineralization and type X collagen localization or capillary invasion and VEGF expression.

Animals↗
PubMed2005

Endocrine regulation of the growth plate.

Longitudinal bone growth occurs at the growth plate by endochondral ossification. Within the growth plate, chondrocyte proliferation, hypertrophy, and cartilage matrix secretion result in chondrogenesis. The newly formed cartilage is invaded by blood vessels and bone cells that remodel the newly formed cartilage into bone tissue. This process of longitudinal bone growth is governed by a complex network of endocrine signals, including growth hormone, insulin-like growth factor I, glucocorticoid, thyroid hormone, estrogen, androgen, vitamin D, and leptin. Many of these signals regulate growth plate function, both by acting locally on growth plate chondrocytes and also indirectly by modulating other endocrine signals in the network. Some of the local effects of hormones are mediated by changes in paracrine factors that control chondrocyte proliferation and differentiation. Many human skeletal growth disorders are caused by abnormalities in the endocrine regulation of the growth plate. This review provides an overview of the endocrine signals that regulate longitudinal bone growth, their interactions, and the mechanisms by which they affect growth plate chondrogenesis.

Androgens↗
PubMed2002

The effects of mechanical loading on the mRNA expression of growth-plate cells.

Bone growth is a complex process involving proliferation, maturation and hypertrophy of chondrocytes in the growth plates. Mechanical forces applied to growing bones alter their longitudinal growth. However, the mechanisms by which chondrocytes modulate longitudinal bone growth are not well understood. This in vitro study investigated the effects of mechanical loading on the mRNA expression pattern of key molecular components of the growth-plate. Short-term static loading was applied to rat proximal tibial growth-plate explants. Various age groups at specific developmental stages were investigated. In situ hybridization was used to assess the mRNA expression of the cells in different zones of the growth-plate. Four key components were investigated: 18s (basic cell metabolism), type II collagen (major extracellular matrix component), type X collagen (matrix component in hypertrophic zone) and PTH-PTHrP receptors (pre-hypertrophic chondrocytes). The spatial variation in the mRNA expression between loaded explants and their contralateral controls was compared to establish: -the sensitivity of the different growth-plate zones to mechanical loading; -the sensitivity of the different developmental stages to loading. Preliminary results indicated that static loading on the growth plate of 80 d.o. rats affects type II and X collagen gene expressions while PTH-PTHrP remains insensitive to static loading. Improved understanding of growth-plate mechanics and the underlying biology is required to provide a scientific basis for the treatment of progressive deformities.

Age Factors↗
PubMed1984

Characterization of growth plate mitochondria.

The growth plate chondrocyte plays a central role in growth plate function. The purpose of this study was to characterize the respiratory and calcium transport properties of isolated mammalian growth plate chondrocytes and mitochondria obtained from these cells and to quantitate the mitochondrial weight and volume fraction in each zone of the growth plate. A new method was developed for isolation of mitochondria from chondrocyte suspensions. Isolated chondrocyte mitochondria demonstrated an eightfold increase in oxygen consumption in response to calcium and a two- to threefold increase in oxygen consumption in response to adenosine diphosphate. Similar responses were observed in chondrocytes treated with digitonin. The mitochondrial protein content of the growth plate and hyaline cartilage chondrocytes is significantly less than hepatocytes. Conversely, the chondrocyte mitochondrial cytochrome aa3 content is similar to mitochondria from a wide variety of sources. A zonal analysis of the growth plate demonstrates an increase in the mitochondrial weight (protein) fraction from the reserve to the hypertrophic zone whereas the mitochondrial volume fraction decreases from the reserve to the hypertrophic zone. The findings of this study emphasize the dependence of chondrocytes on glycolysis as a prime energy source and support the concept that chondrocyte mitochondria have become specialized in the process of matrix calcification.

Animals↗
PubMed1990

Production of collagenase and tissue inhibitor of metalloproteinases (TIMP) by rat growth plates in culture.

Growth plate cartilage from normal and vitamin D-phosphate deficient (-VDP) rats was cultured to study the production of collagenase and tissue inhibitor of metalloproteinases (TIMP) in vitro. All tissues secreted latent collagenase into the medium at a constant rate during the 5 days in culture. Microdissected-VDP growth plates, containing predominatly hypertrophic cells, released up to 8-fold more collagenase into the medium than either intact-VDP or normal growth plates. TIMP was also secreted during the culture, but its rate of production was not as dependent on tissue type as collagenase. The tissue level of collagenase and TIMP before culture was compared with that found in conditioned medium and remnant tissue after culture. During the 5 day culture period microdissected-VDP growth plates, containing predominatly hypertrophic cells, produced 3-times more collagenase/microgram DNA over the starting level than either intact-VDP or normal growth plates. TIMP was never found in tissues after they had been cultured, but was present in all tissues before culture except those containing predominatly hypertrophic cells. The amount of TIMP required to block collagenase was calculated. Growth plates in culture produced enough TIMP to block all collagenase found in the medium and remnant tissue, while extracts of uncultured intact -VDP growth plates, and those divided to contain hypertrophic cells, had an excess of collagenase over TIMP. The results suggest that hypertrophic cells produce far more collagenase than other cells in the growth plate, but all cell types have about the same capacity to synthesize TIMP. As a result, increased collagenase synthesis by hypertrophic cells may surpass increases in TIMP synthesis and lead to collagen removal. This would allow for thinning of the longitudinal septa and expansion of the hypertrophic cells.

Animals↗
PubMed2006

BMP signaling in the cartilage growth plate.

Transforming growth factor-beta (TGF-beta) superfamily members play diverse roles in all aspects of cartilage development and maintenance. It is well established that TGF-betas and bone morphogenetic proteins (BMPs) play distinct roles in the growth plate. This chapter discusses key experiments and experimental approaches that have revealed these roles, and progress toward the identification of previously unsuspected roles. Current understanding of the mechanisms by which different TGF-beta and BMP pathways exert their functions is discussed. Finally attempts to utilize this information to promote cartilage regeneration, and important issues for future research, are outlined.

Animals↗
PubMed1997

Characterization of voltage-sensitive calcium channels in growth plate chondrocytes.

Growth plate chondrocytes (GPCs), cells integrally involved with the process of endochondral bone formation, facilitate Ca2+ infux to provide a source of ion for processes such as Ca2+ signaling and matrix vesicle loading. We hypothesize that this Ca2+ entry into GPCs is achieved through the action of voltage-sensitive Ca2+ channels. This hypothesis was tested by measuring intracellular [Ca2+] changes in fura 2-loaded GPCs that were depolarized by challenge with a K(+)-containing medium. KCl doses between 55 and 95 mM evoked significant Ca2+ responses that were blocked by addition of extracellular EGTA. The Ca2+ response evoked by 95 mM K+ was insensitive to 100 microM doses of nifedipine or nitrendipine, ruling out L-type channel involvement. This finding was corroborated by the observation that 10 microM BAY K 8644 did not activate a Ca2+ response of its own. However, 10 microM Cd2+ significantly inhibited the 95 mM Ks(+)-evoked effects, suggesting N-type channel activity. Use of 1 microM Ni+ in an attempt to block possible T-type channel activity caused nonspecific cellular effects, precluding pharmacological assessment of a possible T-type channel activity. These data (i) provide the first direct evidence for voltage-sensitive Ca2+ channel activity in GPCs and (ii) suggest at least partial facilitation of that activity through N type channels.

Animals↗
PubMed2001

Changes in leucine-rich repeat proteoglycans during maturation of the bovine growth plate.

The primary growth plate of the fetal bovine tibia was studied in order to determine whether changes in the structure, abundance and expression of the leucine-rich repeat proteoglycans were occurring during tissue maturation from reserve cartilage to hypertrophic cartilage. The proteoglycans under study were decorin, biglycan, fibromodulin and lumican. Decorin was readily detectable in both the reserve and proliferating zones of the growth plate, but its abundance decreased markedly in the zones of maturation and hypertrophy where it could not be detected under the same conditions of analysis. In contrast to decorin, fibromodulin and biglycan could be detected throughout the growth plate, though their abundance was decreased in the proliferative and hypertrophic zones. Unlike the other proteoglycans, lumican could not be detected throughout the growth plate. At the message level, the expression of decorin shows a similar trend to that of protein abundance in the extracellular matrix, with its expression dropping markedly in the proliferative and hypertrophic zones. In the case of both biglycan and fibromodulin, message expression continued at a similar level throughout the growth plate. Thus, the leucine-rich repeat proteoglycans are different in the way they behave during growth plate maturation.

Animals↗
PubMed2006

Impaired growth plate chondrogenesis in children with chronic illnesses.

In mammals, statural growth is primarily accomplished by endochondral ossification, which takes place at the growth plate. Growth plate chondrocyte proliferation, hypertrophy/differentiation, apoptosis, and cartilage matrix synthesis all contribute to chondrogenesis or cartilage formation, a process tightly coupled to the simultaneous remodeling of the cartilage into bone at the metaphyseal border of the growth plate. Growth plate chondrogenesis is regulated by the complex interaction of molecular signals acting systemically as well locally within the growth plate. This network is often dysregulated during chronic illnesses, thus resulting in impaired growth plate chondrogenesis and, in turn, growth failure. The principal events responsible for altered growth plate chondrogenesis in chronic illness are inflammation, protein/calorie deprivation, uremia/metabolic acidosis, glucocorticoids, and impaired GH/IGF-I axis.

Acidosis↗
PubMed2006

Inhibition of the proteasomal function in chondrocytes down-regulates growth plate chondrogenesis and longitudinal bone growth.

The proteasome is a large multiprotein complex that processes intracellular proteins functioning as cell cycle regulators and transcription factors. It has been shown that the chymotryptic component of the proteasome is an important regulator of osteoblast differentiation and bone formation, with inhibitors of the proteasome increasing osteoblast differentiation and bone formation. Yet, little is known about the effects of the proteasomal activity in the growth plate. In the present study, we cultured rat metatarsal bones in the presence of proteasome inhibitor I (PSI), a known inhibitor of the chymotrypsin-like activity of the 20S proteasome. PSI suppressed growth plate chondrocyte proliferation and hypertrophy/differentiation, and induced chondrocyte apoptosis. All these cellular effects led to reduced metatarsal linear growth. In cultured chondrocytes, PSI increased the expression of beta-catenin (a negative regulator of chondrogenesis) and reduced the DNA binding of nuclear factor kappaB, a transcription factor that stimulates growth plate chondrogenesis. In conclusion, our findings suggest that the proteasomal activity facilitates growth plate chondrogenesis and, in turn, longitudinal bone growth.

Animals↗
PubMed1987

Morphological analysis and computer-aided, three dimensional reconstruction of chondrocytic columns in rabbit growth plates.

Proximal tibial growth plates of New Zealand white rabbits were serially sectioned in parasagittal and horizontal planes for three dimensional, light microscopic analysis of the chondrocytic columns. A total of 431 columns was analysed. Of these, 258 columns extended through the full height of the growth plate. The remaining columns were considerably shorter, being located either predominantly in the epiphyseal half of the growth plate (100) or in the metaphyseal half of the growth plate (73). The epiphyseal and metaphyseal columns were found in clusters in the plate. Some columns in all three groups had interruptions along their length, while others had duplications. Computer-aided, three dimensional graphic reconstructions were prepared of a selected group of columns. The reconstructions illustrated the variability in the morphology and the dimensions of the neighbouring chondrocytic columns. The observations suggest that chondrocytic columns in rabbit growth plates are replaced regularly and that the small cell zone may play an important role as the cellular source for column renewal.

Animals↗
PubMed1996

In vivo modulation of proliferating cell nuclear antigen in growth plate chondrocytes from normal, hypophysectomized, growth hormone-treated hypophysectomized rats: a comparative immunohistochemical study with image analysis.

Growth hormone (GH) regulates the proliferation and maturation of chondrocytes in the epiphyseal growth plate, in which a temporal dimension is superimposed on the septal organization of the tissue. In this study we investigated the in vivo effects of hypophysectomy (Hypox) and injection of GH into Hypox animals (Hypox + GH) on the proliferative activity of the growth plate chondrocytes. We assessed the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in paraffin-embedded tissues, using monoclonal antibody PC 10 against PCNA combined with immunogold-silver staining. We subjected the immunostained sections to computer-based image analysis by ACAS 570 interactive laser cytometry employing a conventional microscopic light source. Hypox was carried out on 20 rats at 8 weeks of age, half of which received a hypodermic injection of human GH at a dose of 1 IU/kg twice a day for 1 week after the operation. Another group of five rats of the same age were used as normal controls. In normal rats, a distinct PCNA immunoreaction was observed in the proliferative zone, whereas a remarkable diminution of the number of immunoreactive cells in this zone was apparent in Hypox animals. On the other hand, marked hyperplasia of PCNA-positive cells was seen in the proliferative zone of the Hypox + GH rat growth plate. The immunoreactive cells of this zone in Hypox + GH animals exhibited increased nuclear size and staining intensity of PCNA compared with those in normal and Hypox rats. These findings were further confirmed by computer-based image analysis of the specimens in terms of cell integrated value, area, perimeter, and shape factor. These different patterns of PCNA expression may imply that GH specifically promotes the proliferation phase of the chondrocytes in the proliferative zone. The data also suggest that GH influences not only cell replication activity but also cell kinetics of chondrocytes in the growth plate during their lifespan.

Animals↗
PubMed1994

Immunohistochemical analysis of EGF in epiphyseal growth plate from normal, hypophysectomized, and growth hormone-treated hypophysectomized rats.

Epiphyseal growth plate cartilages from the proximal tibia of normal, hypophysectomized, and growth hormone (GH)-treated hypophysectomized rats were subjected to immunohistochemistry for detection of epidermal growth factor (EGF). In the normal growth plate, EGF was distributed mainly in the proliferative zone. Hypophysectomy resulted in considerable atrophy of the chondrocytes and the cartilage matrix (a decreased number of mature-type chondrocytes and a decreased ratio of proliferating to hypertrophic chondrocytes) and a significant diminution of EGF immunoreactivity. Treatment with GH reversed these effects of hypophysectomy, causing an increased thickness of the growth plate and EGF-reactive sites in all chondrocyte layers. The most intense immunostaining for EGF, however, was frequently seen in the nuclei of chondrocytes with flattened appearance. It appears that EGF could be incorporated or synthesized in chondrocytes having marked mitogenic activity. The present results, taken with previous data on EGF involvement in growth of cartilaginous tissue in vivo and in vitro, strongly suggest that EGF-immunoreactive chondrocytes are involved in cartilage proliferation and growth under the specific influence of GH.

Animals↗
PubMed1994

Molecular cloning and expression of bone morphogenetic protein-7 in the chick epiphyseal growth plate.

Longitudinal bone growth occurs in the epiphyseal growth plate and is regulated by a network of paracrine and autocrine interactions. Bone morphogenetic proteins (BMPs) are a family of growth factors whose potent osteogenic properties suggest that they may play an important role within this network, but direct evidence for this is lacking. To address this question, a cDNA encoding chick BMP-7 was cloned from a chick embryo cDNA library. Sequence homology and evolutionary arguments strongly suggested that we had cloned the chicken BMP-7 homologue. Using a reverse transcription-PCR assay, BMP-7 expression was readily detected in bone, growth plate cartilage, brain and heart, and was just detectable in liver, skeletal muscle and adipose tissue. In contrast to the pattern of BMP-7 expression in the rat and mouse, no BMP-7 expression was detected in the chick kidney. In situ hybridization was used to locate the site of BMP-7 expression more precisely within the growth plate. BMP-7 expression was confined to hypertrophic chondrocytes adjacent to and at the tips of the metaphyseal vessels. No expression was detected in the reserve zone or in proliferating chondrocytes. These results point to a specific role for BMP-7 in the growth plate, possibly in osteoblast activation or as a chemotactic agent for the metaphyseal vessels.

Amino Acid Sequence↗
PubMed1995

Serum fractions and related agonists with calcium-mobilizing activity in the bovine growth plate chondrocyte.

Longitudinal growth of bone involves a complex sequence of cellular events in the cartilaginous epiphysis. Whole blood serum has been shown previously to be a potent stimulus to the cells of the growth plate, as demonstrated by its ability to activate the inositol phosphate-calcium second messenger system, resulting in a rise in intracellular Ca2+. By manipulating the preparation of serum to functionally separate it into its constituent parts, we have shown that the processes of platelet lysis and activation of the clotting cascade are responsible for the generation of factors that stimulate this signaling mechanism in isolated bovine growth plate chondrocytes. Through a subsequent trial of bioactive agents generated in these processes, we identified and partially characterized several novel agonists of growth plate chondrocytes:adenosine triphosphate and adenosine diphosphate, the purine energy substrates, and bradykinin, the bioactive peptide generated in a side reaction of the clotting cascade, each induces a rise in intracellular Ca2+ via release from intracellular ion stores. Additionally, the three distinct isoforms of platelet-derived growth factor (AA, AB, and BB), also released on platelet lysis, were compared with respect to their ability to stimulate the inositol phosphate-calcium second messenger system in growth plate chondrocytes.

Adenine Nucleotides↗
PubMed1983

Circulating growth factor studies in growth plate versus resting cartilage in vitro. II. Recognition of growth factors in rat serum.

The growth-promoting effects of GH can be explained in part by the mediation of somatomedins/insulin-like growth factors (IGFs). However, large quantities of the IGFs are required to stimulate growth in vivo, and in some conditions, IGF levels may correlate poorly with GH levels and growth status. These observations suggest that other circulating factors may also be important for growth. We have examined the growth-promoting activity in rat serum, as assessed by stimulation of sulfate and/or thymidine uptake by resting and growth plate cartilage (osteochondral junction) from hypophysectomized rats in vitro. Although stimulation by a low molecular weight somatomedin fraction (approximately 5,000-12,000) accounted for about 90% of serum stimulation of sulfate uptake by resting cartilage, it explained only about 60% of stimulation of the growth plate. Growth plate and resting cartilage appeared equally insensitive to insulin, but the growth plate exhibited reduced sensitivity to inhibitor(s) in diabetic rat serum. Fractionation of normal rat serum by gel filtration at neutral pH revealed comparable stimulation of growth plate and resting cartilage by high molecular weight factors, presumably somatomedins bound to carrier proteins. After gel filtration at acid pH, both growth plate and resting cartilage responded to somatomedins with molecular weights from 5,000-12,000. However, the growth plate also responded to a 12,000-22,000 mol wt factor [Sephadex G-75; 5 X 120 cm; sulfate uptake, 68 +/- 16% above buffer (mean +/- SEM); P less than 0.01] which did not affect resting cartilage (sulfate uptake, 27 +/- 21% above buffer; P = NS). Levels of both the low and higher molecular weight factors were reduced in the serum of hypophysectomized rats. We conclude that circulating growth-promoting activity includes both the low molecular weight somatomedins and a higher molecular weight growth plate growth factor which is not recognized by resting cartilage. Use of the osteochondral junction assay system may permit elucidation of the regulation and nature of this growth factor.

Animals↗
PubMed2000

Cell cycle control in growth plate chondrocytes.

Growth of endochondral bones is regulated by the coordinated proliferation and differentiation of chondrocytes in the epiphyseal growth plates. Many skeletal diseases are caused by pathogenic disruptions of these two processes. While the intracellular mechanisms regulating chondrocyte proliferation and differentiation are poorly understood, recent evidence from studies using genetically altered mice and from experiments in cultured chondrocytes point to a prominent role of cell cycle proteins in this context. This article summarizes our current understanding of the expression, regulation, and function of cell cycle genes in chondrocytes.

Animals↗
PubMed1999

Expression of the components of the insulin-like growth factor axis across the growth-plate.

Linear bone growth occurs as the result of proliferation and differentiation of growth-plate chondrocytes. These two phases of chondrocyte growth are regulated separately, with insulin-like growth factor I (IGF-I) being the primary stimulator of proliferation. We studied the expression of the components of the growth hormone GH/IGF system to learn if this proliferative signal is altered as chondrocytes undergo differentiation. Growth-plate chondrocytes were isolated from fetal cows and fractionated on discontinuous Percoll gradients. Five populations were recovered, ranging from high density cells (proliferative chondrocytes) to low density cells (hypertrophic chondrocytes). Messenger RNAs (mRNAs) were analyzed by a reverse transcriptase/quantitative polymerase chain reaction (RT/qPCR) technique. Results showed that mRNA of IGF-I and IGF-II in proliferative chondrocytes was 32 and five fold more abundant, respectively, than in hypertrophic chondrocytes. Of the four major IGF-I mRNA transcripts, the class 1-Ea transcript was predominant. Messenger RNA levels for IGFBP-3, -4, and -5 were also reduced in hypertrophic chondrocytes. Levels of GH receptor, the type 1 IGF receptor, and IGF binding protein-2 (IGFBP-2) mRNAs were unchanged across the growth-plate. Since IGF-I and -II are potent stimulators of proliferation, the down-regulation of these genes may be necessary in order for hypertrophy to proceed.

Animals↗