The Experts below are selected from a list of 312 Experts worldwide ranked by ideXlab platform
Jeffrey Baron - One of the best experts on this subject based on the ideXlab platform.
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recent research on the Growth Plate recent insights into the regulation of the Growth Plate
Journal of Molecular Endocrinology, 2014Co-Authors: Ola Nilsson, Jeffrey BaronAbstract:For most bones, elongation is driven primarily by chondrogenesis at the Growth Plates. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion, and it is carefully orchestrated by complex networks of local paracrine factors and modulated by endocrine factors. We review here recent advances in the understanding of Growth Plate physiology. These advances include new approaches to study expression patterns of large numbers of genes in the Growth Plate, using microdissection followed by microarray. This approach has been combined with genome-wide association studies to provide insights into the regulation of the human Growth Plate. We also review recent studies elucidating the roles of bone morphogenetic proteins, fibroblast Growth factors, C-type natriuretic peptide, and suppressor of cytokine signaling in the local regulation of Growth Plate chondrogenesis and longitudinal bone Growth.
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Growth Plate senescence and catch up Growth
Endocrine development, 2011Co-Authors: Ola Nilsson, Jeffrey BaronAbstract:Longitudinal bone Growth is rapid in prenatal and early postnatal life, but then slows with age and eventually ceases. This Growth deceleration is caused primarily by a decrease in chondrocyte proliferation, and is associated with other structural, functional, and molecular changes collectively termed Growth Plate senescence. Current evidence suggests that Growth Plate senescence occurs because the progenitor chondrocytes in the resting zone have a limited replicative capacity which is gradually exhausted with increasing cell division. In addition, recent experimental findings from laboratory and clinical studies suggest that Growth Plate senescence explains the phenomenon of catch-up Growth. Growth-inhibiting conditions such as glucocorticoid excess and hypothyroidism delay the program of Growth Plate senescence. Consequently, Growth Plates are less senescent after these conditions resolve and therefore grow more rapidly than is normal for age, resulting in catchup Growth.
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Effects of Glucocorticoids on the Growth Plate
Endocrine development, 2010Co-Authors: Jeffrey BaronAbstract:Glucocorticoids have a direct, inhibitory effect on the Growth Plate, as demonstrated by in vivo and organ culture studies. Glucocorticoids slow longitudinal bone Growth by inhibiting chondrocyte proliferation, hypertrophy, and cartilage matrix synthesis. The molecular mediators of these effects are poorly understood. Glucocorticoids also delay Growth Plate senescence. The decreased rate of senescence appears to be a consequence of the Growth inhibition and, in particular, may occur because glucocorticoids slow proliferation of stem-like cells in the resting zone and therefore conserve the limited proliferative capacity of these cells. This slowing of senescence appears to explain the phenomenon of catch-up Growth following transient glucocorticoid exposure. After the exposure, the Growth Plate is less senescent, and therefore grows more rapidly than is normal for age. Glucocorticoids cause Growth inhibition and subsequent catch-up Growth not only in terms of longitudinal bone Growth at the Growth Plate but also in terms of cross-sectional bone Growth at the periosteum. Whether the underlying mechanisms are analogous to those at the Growth Plate is not known.
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Growth-inhibiting conditions slow Growth Plate senescence
Journal of Endocrinology, 2010Co-Authors: Patricia Forcinito, Anenisia C. Andrade, Jeffrey Baron, Gabriela P. Finkielstain, Ola NilssonAbstract:The mammalian Growth Plate undergoes programed senescence during juvenile life, causing skeletal Growth to slow with age. We previously found that hypothyroidism in rats slowed both Growth Plate chondrocyte proliferation and Growth Plate senescence, suggesting that senescence is not dependent on age per se but rather on chondrocyte proliferation. However, one alternative explanation is that the observed slowing of Growth Plate senescence is a specific consequence of hypothyroidism. We reasoned that, if delayed senescence is a general consequence of Growth inhibition, rather than a specific result of hypothyroidism, then senescence would also be slowed by other Growth-inhibiting conditions. In this study, we therefore used tryptophan deficiency to temporarily inhibit Growth in newborn rats for 4 weeks. We then allowed the animals to recover and studied the effects on Growth Plate senescence. We found that structural, functional, and molecular markers of Growth Plate senescence were delayed by prior tryptophan deficiency, indicating that the developmental program of senescence had occurred more slowly during the period of Growth inhibition. Taken together with previous studies in hypothyroid rats, our findings support the hypothesis that delayed senescence is a general consequence of Growth inhibition and hence that Growth Plate senescence is not simply a function of time per se but rather depends on Growth.
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Fibroblast Growth factor expression in the postnatal Growth Plate.
Bone, 2006Co-Authors: Jacob E. Lazarus, Ola Nilsson, Anenisia C. Andrade, Anita Hegde, Jeffrey BaronAbstract:Abstract 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.
Ola Nilsson - One of the best experts on this subject based on the ideXlab platform.
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recent research on the Growth Plate recent insights into the regulation of the Growth Plate
Journal of Molecular Endocrinology, 2014Co-Authors: Ola Nilsson, Jeffrey BaronAbstract:For most bones, elongation is driven primarily by chondrogenesis at the Growth Plates. This process results from chondrocyte proliferation, hypertrophy, and extracellular matrix secretion, and it is carefully orchestrated by complex networks of local paracrine factors and modulated by endocrine factors. We review here recent advances in the understanding of Growth Plate physiology. These advances include new approaches to study expression patterns of large numbers of genes in the Growth Plate, using microdissection followed by microarray. This approach has been combined with genome-wide association studies to provide insights into the regulation of the human Growth Plate. We also review recent studies elucidating the roles of bone morphogenetic proteins, fibroblast Growth factors, C-type natriuretic peptide, and suppressor of cytokine signaling in the local regulation of Growth Plate chondrogenesis and longitudinal bone Growth.
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Local regulation of Growth Plate cartilage.
Endocrine development, 2011Co-Authors: Stephan-stanislaw Späth, Anenisia C. Andrade, Michael Chau, Ola NilssonAbstract:Elongation of bones primarily occurs by endochondral ossification at the Growth Plate. In the Growth Plate, stem-like cells in the resting zone differentiate into rapidly dividing chondrocytes in the
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Growth Plate senescence and catch up Growth
Endocrine development, 2011Co-Authors: Ola Nilsson, Jeffrey BaronAbstract:Longitudinal bone Growth is rapid in prenatal and early postnatal life, but then slows with age and eventually ceases. This Growth deceleration is caused primarily by a decrease in chondrocyte proliferation, and is associated with other structural, functional, and molecular changes collectively termed Growth Plate senescence. Current evidence suggests that Growth Plate senescence occurs because the progenitor chondrocytes in the resting zone have a limited replicative capacity which is gradually exhausted with increasing cell division. In addition, recent experimental findings from laboratory and clinical studies suggest that Growth Plate senescence explains the phenomenon of catch-up Growth. Growth-inhibiting conditions such as glucocorticoid excess and hypothyroidism delay the program of Growth Plate senescence. Consequently, Growth Plates are less senescent after these conditions resolve and therefore grow more rapidly than is normal for age, resulting in catchup Growth.
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Growth-inhibiting conditions slow Growth Plate senescence
Journal of Endocrinology, 2010Co-Authors: Patricia Forcinito, Anenisia C. Andrade, Jeffrey Baron, Gabriela P. Finkielstain, Ola NilssonAbstract:The mammalian Growth Plate undergoes programed senescence during juvenile life, causing skeletal Growth to slow with age. We previously found that hypothyroidism in rats slowed both Growth Plate chondrocyte proliferation and Growth Plate senescence, suggesting that senescence is not dependent on age per se but rather on chondrocyte proliferation. However, one alternative explanation is that the observed slowing of Growth Plate senescence is a specific consequence of hypothyroidism. We reasoned that, if delayed senescence is a general consequence of Growth inhibition, rather than a specific result of hypothyroidism, then senescence would also be slowed by other Growth-inhibiting conditions. In this study, we therefore used tryptophan deficiency to temporarily inhibit Growth in newborn rats for 4 weeks. We then allowed the animals to recover and studied the effects on Growth Plate senescence. We found that structural, functional, and molecular markers of Growth Plate senescence were delayed by prior tryptophan deficiency, indicating that the developmental program of senescence had occurred more slowly during the period of Growth inhibition. Taken together with previous studies in hypothyroid rats, our findings support the hypothesis that delayed senescence is a general consequence of Growth inhibition and hence that Growth Plate senescence is not simply a function of time per se but rather depends on Growth.
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Fibroblast Growth factor expression in the postnatal Growth Plate.
Bone, 2006Co-Authors: Jacob E. Lazarus, Ola Nilsson, Anenisia C. Andrade, Anita Hegde, Jeffrey BaronAbstract:Abstract 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.
Veronica Abad - One of the best experts on this subject based on the ideXlab platform.
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the role of the resting zone in Growth Plate chondrogenesis
Endocrinology, 2002Co-Authors: Veronica Abad, Ola Nilsson, John Bacher, Kevin M Barnes, Jodi L Meyers, Martina Weise, Rachel I Gafni, Jeffrey BaronAbstract:In mammals, Growth of long bones occurs at the Growth Plate, a cartilage structure that contains three principal layers: the resting, proliferative, and hypertrophic zones. The function of the resting zone is not well understood. We removed the proliferative and hypertrophic zones from the rabbit distal ulnar Growth Plate in vivo, leaving only the resting zone. Within 1 wk, a complete proliferative and hypertrophic zone often regenerated. Next, we manipulated Growth Plates in vivo to place resting zone cartilage ectopically alongside the proliferative columns. Ectopic resting zone cartilage induced a 90degree shift in the orientation of nearby proliferative zone chondrocytes and seemed to inhibit their hypertrophic differentiation. Our findings suggest that resting zone cartilage makes important contributions to endochondral bone formation at the Growth Plate: 1) it contains stem-like cells that give rise to clones of proliferative chondrocytes; 2) it produces a Growth Plate-orienting factor, a morphogen, that directs the alignment of the proliferative clones into columns parallel to the long axis of the bone; and 3) it may also produce a morphogen that inhibits terminal differentiation of nearby proliferative zone chondrocytes and thus may be partially responsible for the organization of the Growth Plate into distinct zones of proliferation and hypertrophy. (Endocrinology 143: 1851–1857, 2002)
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effects of estrogen on Growth Plate senescence and epiphyseal fusion
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Martina Weise, Kevin M Barnes, Veronica Abad, Stacy Delevi, Rachel I Gafni, Jeffrey BaronAbstract:Abstract Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes this phenomenon. Juvenile ovariectomized female rabbits received either 70 μg/kg estradiol cypionate or vehicle i.m. once a week. Growth Plates from the proximal tibia, distal tibia, and distal femur were analyzed after 2, 4, 6, or 8 weeks of treatment. In vehicle-treated animals, there was a gradual senescent decline in tibial Growth rate, rate of chondrocyte proliferation, Growth Plate height, number of proliferative chondrocytes, number of hypertrophic chondrocytes, size of terminal hypertrophic chondrocytes, and column density. Estrogen treatment accelerated the senescent decline in all of these parameters. In senescent Growth Plates, epiphyseal fusion was observed to be an abrupt event in which all remaining chondrocytes were rapidly replaced by bone elements. Fusion occurred when the rate of chondrocyte proliferation approached zero. Estrogen caused this proliferative exhaustion and fusion to occur earlier. Our data suggest that (i) epiphyseal fusion is triggered when the proliferative potential of Growth Plate chondrocytes is exhausted; and (ii) estrogen does not induce Growth Plate ossification directly; instead, estrogen accelerates the programmed senescence of the Growth Plate, thus causing earlier proliferative exhaustion and consequently earlier fusion.
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regulation of Growth Plate chondrogenesis by bone morphogenetic protein 21
Endocrinology, 2001Co-Authors: Francesco De Luca, Kevin M Barnes, Veronica Abad, Jennifer A. Uyeda, Stacy Delevi, Teresa Palese, Veronica Mericq, Jeffrey BaronAbstract:Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the Growth Plate, also regulates Growth Plate chondrogenesis and longitudinal bone Growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal Growth. As the rate of longitudinal bone Growth depends primarily on the rate of Growth Plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the Growth Plate, as assessed by [3H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by 35SO4 incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-...
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Determinants of Spatial Polarity in the Growth Plate
Endocrinology, 1999Co-Authors: Veronica Abad, Francesco De Luca, Jennifer A. Uyeda, H. Thomas Temple, Jeffrey BaronAbstract:Growth of long bones occurs at the Growth Plate, a layer of cartilage that separates the epiphysis from the metaphysis. Growth Plate exhibits spatial polarity. Proliferative chondrocytes undergo terminal differentiation when they approach the metaphyseal, but not the epiphyseal, border of the Growth Plate. The adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal, blood vessels and bone cells invade the adjacent Growth Plate, remodeling it into bone. As a result, the metaphysis, but not the epiphysis, elongates over time. To determine whether cartilage polarity determines bone polarity and/or whether bone polarity determines cartilage polarity, rabbit distal ulnar Growth Plates were excised, inverted, and reimplanted in their original beds. Thus, cartilage polarity was inverted relative to bone polarity. Histological examination showed that the inverted cartilage polarity was maintained over time. In contrast, the polarity of the adjacent bone reversed after surgery, to match that ...
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Determinants of Spatial Polarity in the Growth Plate |[bull]| 394
Pediatric Research, 1998Co-Authors: Veronica Abad, Francesco De Luca, Jennifer A. Uyeda, H. Thomas Temple, Jeffrey BaronAbstract:Growth of long bones occurs at the Growth Plate, a layer of cartilage that separates the epiphysis from the metaphysis. Growth Plate exhibits spatial polarity. Proliferative chondrocytes undergo terminal differentiation when they approach the metaphyseal, but not the epiphyseal, border of the Growth Plate. The adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal, blood vessels and bone cells invade adjacent Growth Plate, remodeling it into bone. As a result, the metaphysis, but not the epiphysis, elongates over time.
Kevin M Barnes - One of the best experts on this subject based on the ideXlab platform.
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depletion of resting zone chondrocytes during Growth Plate senescence
Journal of Endocrinology, 2006Co-Authors: Lenneke Schrier, Ola Nilsson, Sandra P Ferns, Kevin M Barnes, J Emons, Eric I Newman, Jeffrey BaronAbstract:With age, the Growth Plate undergoes senescent changes that cause linear bone Growth to slow and finally cease. Based on previous indirect evidence, we hypothesized that this senescent decline occurs because Growth Plate stem-like cells, located in the resting zone, have a finite proliferative capacity that is gradually depleted. Consistent with this hypothesis, we found that the proliferation rate in rabbit resting zone chondrocytes (assessed by continuous 5-bromo-2-deoxy-uridine labeling) decreases with age, as does the number of resting zone chondrocytes per area of Growth Plate. Glucocorticoid excess slows Growth Plate senescence. To explain this effect, we hypothesized that glucocorticoid inhibits resting zone chondrocyte proliferation, thus conserving their proliferative capacity. Consistent with this hypothesis, we found that dexamethasone treatment decreased the proliferation rate of rabbit resting zone chondrocytes and slowed the numerical depletion of these cells. Estrogen is known to accelerate Growth Plate senescence. However, we found that estradiol cypionate treatment slowed resting zone chondrocyte proliferation. Our findings support the hypotheses that Growth Plate senescence is caused by qualitative and quantitative depletion of stem-like cells in the resting zone and that Growth-inhibiting conditions, such as glucocorticoid excess, slow senescence by slowing resting zone chondrocyte proliferation and slowing the numerical depletion of these cells, thereby conserving the proliferative capacity of the Growth Plate. We speculate that estrogen might accelerate senescence by a proliferation-independent mechanism, or by increasing the loss of proliferative capacity per cell cycle.
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Growth Plate senescence is associated with loss of DNA methylation
Journal of Endocrinology, 2005Co-Authors: Ola Nilsson, Lenneke Schrier, Sandra P Ferns, Kevin M Barnes, Robert D. Mitchum, James F. Troendle, Jeffrey BaronAbstract:The overall body size of vertebrates is primarily determined by longitudinal bone Growth at the Growth Plate. With age, the Growth Plate undergoes programmed senescence, causing longitudinal bone Growth to slow and eventually cease. Indirect evidence suggests that Growth Plate senescence occurs because stem-like cells in the Growth Plate resting zone have a finite proliferative capacity that is gradually exhausted. Similar limits on replication have been observed when many types of animal cells are placed in cell culture, an effect known as the Hayflick phenomenon. However, we found that the number of population doublings of rabbit resting zone chondrocytes in culture did not depend on the age of the animal from which the cells were harvested, suggesting that the mechanisms limiting replicative capacity of Growth Plate chondrocytes in vivo are distinct from those in vitro. We also observed that the level of DNA methylation in resting zone chondrocytes decreased with age in vivo. This loss of methylation appeared to occur specifically with the slow proliferation of resting zone chondrocytes in vivo and was not observed with the rapid proliferation of proliferative zone chondrocytes in vivo (i.e. the level of DNA methylation did not change from the resting zone to the hypertrophic zone), with proliferation of chondrocytes in vitro, or with Growth of the liver in vivo. Thus, the overall level of DNA methylation decreases during Growth Plate senescence. This finding is consistent with the hypothesis that the mechanism limiting replication of Growth Plate chondrocytes in vivo involves loss of DNA methylation and, thus, loss of DNA methylation might be a fundamental biological mechanism that limits longitudinal bone Growth in mammals, thereby determining the overall adult size of the organism.
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the role of the resting zone in Growth Plate chondrogenesis
Endocrinology, 2002Co-Authors: Veronica Abad, Ola Nilsson, John Bacher, Kevin M Barnes, Jodi L Meyers, Martina Weise, Rachel I Gafni, Jeffrey BaronAbstract:In mammals, Growth of long bones occurs at the Growth Plate, a cartilage structure that contains three principal layers: the resting, proliferative, and hypertrophic zones. The function of the resting zone is not well understood. We removed the proliferative and hypertrophic zones from the rabbit distal ulnar Growth Plate in vivo, leaving only the resting zone. Within 1 wk, a complete proliferative and hypertrophic zone often regenerated. Next, we manipulated Growth Plates in vivo to place resting zone cartilage ectopically alongside the proliferative columns. Ectopic resting zone cartilage induced a 90degree shift in the orientation of nearby proliferative zone chondrocytes and seemed to inhibit their hypertrophic differentiation. Our findings suggest that resting zone cartilage makes important contributions to endochondral bone formation at the Growth Plate: 1) it contains stem-like cells that give rise to clones of proliferative chondrocytes; 2) it produces a Growth Plate-orienting factor, a morphogen, that directs the alignment of the proliferative clones into columns parallel to the long axis of the bone; and 3) it may also produce a morphogen that inhibits terminal differentiation of nearby proliferative zone chondrocytes and thus may be partially responsible for the organization of the Growth Plate into distinct zones of proliferation and hypertrophy. (Endocrinology 143: 1851–1857, 2002)
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effects of estrogen on Growth Plate senescence and epiphyseal fusion
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Martina Weise, Kevin M Barnes, Veronica Abad, Stacy Delevi, Rachel I Gafni, Jeffrey BaronAbstract:Abstract Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes this phenomenon. Juvenile ovariectomized female rabbits received either 70 μg/kg estradiol cypionate or vehicle i.m. once a week. Growth Plates from the proximal tibia, distal tibia, and distal femur were analyzed after 2, 4, 6, or 8 weeks of treatment. In vehicle-treated animals, there was a gradual senescent decline in tibial Growth rate, rate of chondrocyte proliferation, Growth Plate height, number of proliferative chondrocytes, number of hypertrophic chondrocytes, size of terminal hypertrophic chondrocytes, and column density. Estrogen treatment accelerated the senescent decline in all of these parameters. In senescent Growth Plates, epiphyseal fusion was observed to be an abrupt event in which all remaining chondrocytes were rapidly replaced by bone elements. Fusion occurred when the rate of chondrocyte proliferation approached zero. Estrogen caused this proliferative exhaustion and fusion to occur earlier. Our data suggest that (i) epiphyseal fusion is triggered when the proliferative potential of Growth Plate chondrocytes is exhausted; and (ii) estrogen does not induce Growth Plate ossification directly; instead, estrogen accelerates the programmed senescence of the Growth Plate, thus causing earlier proliferative exhaustion and consequently earlier fusion.
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regulation of Growth Plate chondrogenesis by bone morphogenetic protein 21
Endocrinology, 2001Co-Authors: Francesco De Luca, Kevin M Barnes, Veronica Abad, Jennifer A. Uyeda, Stacy Delevi, Teresa Palese, Veronica Mericq, Jeffrey BaronAbstract:Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the Growth Plate, also regulates Growth Plate chondrogenesis and longitudinal bone Growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal Growth. As the rate of longitudinal bone Growth depends primarily on the rate of Growth Plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the Growth Plate, as assessed by [3H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by 35SO4 incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-...
Francesco De Luca - One of the best experts on this subject based on the ideXlab platform.
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Impaired Growth Plate Chondrogenesis in Children with Chronic Illnesses
Pediatric Research, 2006Co-Authors: Francesco De LucaAbstract: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.
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endocrine regulation of the Growth Plate
Hormone Research in Paediatrics, 2005Co-Authors: Ola Nilsson, Rose Marino, Francesco De Luca, Moshe Phillip, Jeffrey BaronAbstract:Longitudinal bone Growth occurs at the Growth Plate by endochondral ossification. Within the Growth Plate, chondrocyte proliferation, hypertrophy, and cartilage matrix secretion result in chondrogenes
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regulation of Growth Plate chondrogenesis by bone morphogenetic protein 21
Endocrinology, 2001Co-Authors: Francesco De Luca, Kevin M Barnes, Veronica Abad, Jennifer A. Uyeda, Stacy Delevi, Teresa Palese, Veronica Mericq, Jeffrey BaronAbstract:Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the Growth Plate, also regulates Growth Plate chondrogenesis and longitudinal bone Growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal Growth. As the rate of longitudinal bone Growth depends primarily on the rate of Growth Plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the Growth Plate, as assessed by [3H]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by 35SO4 incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-...
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Determinants of Spatial Polarity in the Growth Plate
Endocrinology, 1999Co-Authors: Veronica Abad, Francesco De Luca, Jennifer A. Uyeda, H. Thomas Temple, Jeffrey BaronAbstract:Growth of long bones occurs at the Growth Plate, a layer of cartilage that separates the epiphysis from the metaphysis. Growth Plate exhibits spatial polarity. Proliferative chondrocytes undergo terminal differentiation when they approach the metaphyseal, but not the epiphyseal, border of the Growth Plate. The adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal, blood vessels and bone cells invade the adjacent Growth Plate, remodeling it into bone. As a result, the metaphysis, but not the epiphysis, elongates over time. To determine whether cartilage polarity determines bone polarity and/or whether bone polarity determines cartilage polarity, rabbit distal ulnar Growth Plates were excised, inverted, and reimplanted in their original beds. Thus, cartilage polarity was inverted relative to bone polarity. Histological examination showed that the inverted cartilage polarity was maintained over time. In contrast, the polarity of the adjacent bone reversed after surgery, to match that ...
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Determinants of Spatial Polarity in the Growth Plate |[bull]| 394
Pediatric Research, 1998Co-Authors: Veronica Abad, Francesco De Luca, Jennifer A. Uyeda, H. Thomas Temple, Jeffrey BaronAbstract:Growth of long bones occurs at the Growth Plate, a layer of cartilage that separates the epiphysis from the metaphysis. Growth Plate exhibits spatial polarity. Proliferative chondrocytes undergo terminal differentiation when they approach the metaphyseal, but not the epiphyseal, border of the Growth Plate. The adjacent bone also exhibits spatial polarity. Metaphyseal, but not epiphyseal, blood vessels and bone cells invade adjacent Growth Plate, remodeling it into bone. As a result, the metaphysis, but not the epiphysis, elongates over time.
