Patterson-Buckendahl P, Kvetnansky R, Fukuhara K, Cizza G, Cann C
Division of Natural Sciences and Mathematics, Richard Stockton College, Pomona, NJ 08240, USA.
Bone. 1995 Nov;17(5):467-72. doi: 10.1016/8756-3282(95)00281-x.
Osteocalcin (OC), an extracellular calcium-binding protein of bone origin, is synthesized by osteoblasts and binds with high specificity to bone mineral crystals. A small, but relatively consistent portion of newly synthesized OC which is released to circulation has been well correlated with histological indices of osteoblastic activity. Synthesis of OC is regulated by numerous hormones including glucocorticoids. We previously reported that mild mental stressors such as cage change or cold exposure decreased rat plasma OC by up to 40% within 1 h. A similar response was induced in a time- and dose-related manner by injection of physiological levels of corticosterone (CS), the active glucocorticoid in rats. Prone immobilization by foot restraint of conscious rats for up to 2 h (IMMO) is a well-characterized model of classic "fight-or-flight" response. This model induces an immediate and prolonged elevation of CS, as well as the catecholamines epinephrine (E) and norepinephrine (NE). In marked contrast to milder stressors, immobilization induced an immediate increase of plasma OC, greater than 50% within 5-20 min, which returned toward normal after 2 h of restraint. Selective ablation of the hormones by adrenal medulectomy, adrenalectomy, or blockade of sympathetic ganglia did not abolish the initial rapid rise of plasma OC. Even before IMMO, plasma OC was increased by about 50% in the absence of sympathetic neural function or adrenal CS production. The presence of both CS and NE, but not E, was required to return plasma OC concentrations to basal levels. This strongly suggests interaction of CS and NE to regulate plasma OC and its release from bone. As expected, prior cold exposure lowered plasma OC, but did not abolish a subsequent increase in response to IMMO, nor did IMMO repeated daily for 7 days. The stimulus for the initial rapid elevation of OC is unknown, but likely to be of importance in the role OC plays in response to stress. Further investigation of the OC under mental stress should help to understand the function of this abundant and highly conserved bone protein.
骨钙素（OC）是一种源自骨骼的细胞外钙结合蛋白，由成骨细胞合成，并与骨矿物质晶体高度特异性结合。新合成的OC释放到循环中的一小部分，但相对稳定，已与成骨细胞活性的组织学指标密切相关。OC的合成受多种激素调节，包括糖皮质激素。我们之前报道，轻度精神应激源，如笼子更换或冷暴露，可在1小时内使大鼠血浆OC降低多达40%。注射生理水平的皮质酮（CS）（大鼠体内的活性糖皮质激素）以时间和剂量相关的方式诱导了类似的反应。将清醒大鼠足部束缚长达2小时（IMMO）的俯卧固定是经典“战斗或逃跑”反应的一个特征明确的模型。该模型诱导CS以及儿茶酚胺肾上腺素（E）和去甲肾上腺素（NE）立即且持续升高。与较轻的应激源形成鲜明对比的是，固定诱导血浆OC立即增加，在5 - 20分钟内增加超过50%，束缚2小时后恢复正常。通过肾上腺髓质切除术、肾上腺切除术或交感神经节阻断选择性去除激素并不能消除血浆OC最初的快速升高。即使在IMMO之前，在没有交感神经功能或肾上腺CS产生的情况下，血浆OC也增加了约50%。需要同时存在CS和NE，但不需要E，才能使血浆OC浓度恢复到基础水平。这强烈表明CS和NE相互作用以调节血浆OC及其从骨骼中的释放。正如预期的那样，先前的冷暴露降低了血浆OC，但并没有消除随后对IMMO的反应增加，每天重复IMMO 7天也没有消除。OC最初快速升高的刺激因素尚不清楚，但可能在OC对应激的反应中起重要作用。对精神应激下OC的进一步研究应有助于理解这种丰富且高度保守的骨蛋白的功能。
