Control of Bone Growth in Rats

Kember, N. F.; Walker, K. V. R.

doi:10.1038/229428a0

Cited by 117 publications

(82 citation statements)

References 5 publications

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“…These functional senescent changes are accompanied by structural senescent changes. There is a gradual decline in the overall growth plate height, proliferative zone height, hypertrophic zone height, size of hypertrophic chondrocytes, and column density (Kember & Walker 1971, Walker & Kember 1972a,b, Kember 1973, Masoud et al 1986, Hunziker & Schenk 1989, Farquharson & Loveridge 1990. The growth plate undergoes ossification as the final step in the senescence program.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Nilsson

Abad²,

Chrysis³

et al. 2002

Journal of Endocrinology

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Estrogen regulates skeletal growth and promotes epiphyseal fusion. To explore the mechanisms underlying these effects we investigated the expression of estrogen receptor-(ER ) and -(ER ) in rat and rabbit growth plates during postnatal development, using immunohistochemistry. Immunoreactivity for ER and ER was observed in resting zone and proliferative zone chondrocytes at all ages studied for both rat (7, 14, 28 and 70 days of age) and rabbit (1, 7, 28 and 120 days of age). In the rat distal humerus and the rabbit proximal tibia, expression of both receptors in the hypertrophic zone was minimal at early ages, increasing only at the last time point prior to epiphyseal fusion. Expression was rarely seen in the hypertrophic zone of the rat proximal tibia, a growth plate that does not fuse until late in life. Therefore, we conclude that ER and ER are both expressed in the mammalian growth plate. The temporal and anatomical pattern suggests that ER expression in the hypertrophic zone in particular may play a role in epiphyseal fusion.

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Section: Introductionmentioning

confidence: 99%

“…With increasing age, the growth plate undergoes structural and functional changes. The rate of longitudinal bone growth decreases due, in large part, to a decline in chondrocyte proliferation (Kember & Walker 1971). However, physiological cell death (Roach & Clarke 1999) may also contribute to the senescence process.…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Nilsson

Abad²,

Chrysis³

et al. 2002

Journal of Endocrinology

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show abstract

“…In other mammals, a similar dramatic decline in growth rate occurs, but without a superimposed pubertal growth spurt. Kember and Walker (1971) showed that this senescent decline in growth rate is due, in large part, to a decrease in the proliferation rate of growth plate chondrocytes. These functional senescent changes are accompanied by structural senescent changes.…”

Section: Introductionmentioning

confidence: 99%

“…These functional senescent changes are accompanied by structural senescent changes. There is a gradual decline in the overall growth plate height, proliferative zone height, hypertrophic zone height, size of hypertrophic chondrocytes, and column density (Kember & Walker 1971, Kember 1973, Masoud et al 1986a, Masoud et al 1986b, Walker & Kember 1972a, Walker & Kember 1972b, Hunziker & Schenk 1989, Farquharson & Loveridge 1990. The growth plate undergoes ossification as the final step in the senescence program .…”

Section: Introductionmentioning

confidence: 99%

Depletion of resting zone chondrocytes during growth plate senescence

Schrier

Ferns²,

Barnes³

et al. 2006

Journal of Endocrinology

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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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“…16,17,[34][35][36] In normal growth plates under steady-state conditions, the number of new proliferative cells produced by mitotic division approximates the number of cells lost to hypertrophic terminal differentiation and turnover at the metaphyseal chondro-osseous junction. 16,[37][38][39][40][41][42] Radiation therapy kills a significant population of proliferative cells, therefore reducing the population of cells available to undergo hypertrophic enlargement during terminal differentiation, resulting in discrepant physeal elongation.…”

Section: Discussionmentioning

confidence: 99%

Restoration of growth plate function following radiotherapy is driven by increased proliferative and synthetic activity of expansions of chondrocytic clones

Horton

Margulies

Strauss

et al. 2006

Journal Orthopaedic Research

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Radiation therapy encompassing an active epiphysis can negatively impact the potential for bone growth by disrupting cell-cycle progression and accelerating apoptosis and terminal differentiation in physeal chondrocytes. Despite functional derangement following radiation exposure, the irradiated growth plate retains a capacity for regeneration and recovery of growth. The purpose of this study was to characterize the initial sequence of events leading to functional growth recovery in irradiated weanling rat growth plates. We hypothesized that growth in an irradiated epiphysis would be partially restored due to the expansion of chondrocytic clones. Stereological histomorphometry was used to compare chondrocytic cell and matrix turnover between the first and second week following irradiation, and to determine the relative contribution of each of the cellular and extracellular matrix (ECM) compartments to growth. We found that restoration of growth in the irradiated limb was strongly associated with the proliferative activity and production of ECM by these chondrocytic clones, as they expand in average volume, but not in numerical density. We conclude that chondrocytes forming expansive clones and exhibiting increased mitotic and matrix synthesis activity initiate the early restoration of function in the irradiated growth plate, and would be a logical target for strategies to restore full growth potential. ß

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Control of Bone Growth in Rats

Cited by 117 publications

References 5 publications

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Estrogen receptor-alpha and -beta are expressed throughout postnatal development in the rat and rabbit growth plate

Depletion of resting zone chondrocytes during growth plate senescence

Restoration of growth plate function following radiotherapy is driven by increased proliferative and synthetic activity of expansions of chondrocytic clones

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