Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis
Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis
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DOI：
10.1242/jeb.02185
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发表时间：
2006-05-01
影响因子：
2.8
通讯作者：
McGee, ME
中科院分区：
文献类型：
--
作者：
Donahue, SW;Galley, SA;McGee, ME
骨的机械卸载导致骨形成和吸收的失衡，导致骨丢失和增加骨折的风险。黑熊(Ursus Americanus)在冬眠期间最长可达六个月不活动，但骨骼矿物质含量和强度不会因停用或老化而减少。为了测试冬眠熊是否有预防废用性骨质疏松症的生物学机制，我们测量了与骨骼代谢有关的激素和生长因子的血清浓度，并将它们与骨形成标志物(骨钙素)的血清浓度相关联。血清是从黑熊身上获得的，持续时间为7个月，包括活动期和静止期。在冬眠期间，骨吸收和形成标志物都增加，这表明在不活动期间发生了高的骨转换。然而，骨形成与骨吸收似乎是平衡的。甲状旁腺激素在冬眠季节(P=0.35)和冬眠后季节(P=0.006)均高于冬眠前水平。与冬眠前和冬眠期间相比，冬眠后血清瘦素水平较低(P<；0.004)。胰岛素样生长因子-I在冬眠期间较冬眠前下降(P<；0.0001)，在再活动时达到最高值。3个季节之间25-OH维生素D含量差异无统计学意义(P=0.64)。血清骨钙素(骨形成标记物)与甲状旁腺激素显著相关，但与瘦素、IGF-I或25-羟基维生素D无关。骨钙素和甲状旁腺素在合并所有季节的样本和仅考虑冬眠样本时呈正相关，这增加了甲状旁腺素的合成代谢作用有助于维持骨形成以防止废用性骨质疏松的可能性。不同季节(冬眠期与活动期)的熊血清对MC3T3成骨细胞前列腺素E-2(PGE(2))的释放有显著影响。PGE2释放的季节变化趋势与血清IGF-I的季节变化趋势相似。由于PGE2和IGF-I都与胶原骨的形成有关，循环因子的季节性变化可能会影响熊体内的IGF-I水平和体外成骨细胞的PGE2释放。假设脑室内的瘦素也有类似的下降，冬眠唤醒后血清瘦素的显著下降可能会促进再动员过程中的骨形成。这些发现支持这样一种观点，即循环分子浓度的季节性变化有助于调节骨骼形成活动，可能对预防熊的废用性骨质疏松症很重要。
Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears ( Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker ( osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (P < 0.004) post-hibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I ( IGF-I) decreased (P < 0.0001) during hibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E-2 (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE2 release showed trends similar to the seasonal changes in serum IGF-I. Since both PGE2 and IGF-I are associated with collagenous bone formation, it is possible that seasonal changes in a circulating factor influence IGF-I levels in vivo in bears and PGE2 release in osteoblastic cells in vitro. The significant decrease in serum leptin following arousal from hibernation may promote bone formation during remobilization, assuming there is a similar decrease in intracerebroventricular leptin. These findings support the idea that seasonal changes in the concentration of circulating molecules help regulate bone formation activity and may be important for preventing disuse osteoporosis in bears.