Schrier Lenneke, Ferns Sandra P, Barnes Kevin M, Emons Joyce A M, Newman Eric I, Nilsson Ola, Baron Jeffrey
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, CRC, Room 1-3330, 10 Center Drive, MSC 1103, Bethesda, Maryland 20892, USA.
J Endocrinol. 2006 Apr;189(1):27-36. doi: 10.1677/joe.1.06489.
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.
随着年龄增长，生长板会发生衰老变化，导致线性骨生长减缓并最终停止。基于先前的间接证据，我们推测这种衰老衰退的发生是因为位于静止区的生长板干细胞样细胞具有有限的增殖能力，且该能力会逐渐耗尽。与这一假设相符，我们发现兔静止区软骨细胞的增殖率（通过连续5-溴-2'-脱氧尿苷标记评估）随年龄增长而降低，生长板单位面积内静止区软骨细胞的数量也如此。糖皮质激素过多会减缓生长板衰老。为解释这种作用，我们推测糖皮质激素会抑制静止区软骨细胞增殖，从而保留它们的增殖能力。与这一假设相符，我们发现地塞米松处理降低了兔静止区软骨细胞的增殖率，并减缓了这些细胞数量的减少。已知雌激素会加速生长板衰老。然而，我们发现环戊丙酸雌二醇处理减缓了静止区软骨细胞增殖。我们的研究结果支持以下假设：生长板衰老由静止区干细胞样细胞的质和量的耗竭引起，而诸如糖皮质激素过多等生长抑制条件通过减缓静止区软骨细胞增殖和减缓这些细胞数量的减少来延缓衰老，从而保留生长板的增殖能力。我们推测雌激素可能通过非增殖依赖机制或通过增加每个细胞周期增殖能力的丧失来加速衰老。
