Delaisse J M, Eeckhout Y, Vaes G
Laboratoire de Chimie Physiologique, Université de Louvain, Bruxelles, Belgium.
Endocrinology. 1988 Jul;123(1):264-76. doi: 10.1210/endo-123-1-264.
The participation of collagenase in bone resorption has been investigated by assaying the procollagenase extracted from fetal mouse calvaria cultured under a variety of conditions, and by evaluating its ability to degrade bone collagen. Procollagenase was found in two separate pools, one requiring demineralization for its extraction, the other not. Culturing the bones with PTH, 1,25-dihydroxyvitamin D3, prostaglandin E2, interleukin-1, tumor necrosis factor-alpha, catabolin, retinoic acid, or endotoxin (but not with heparin) induced resorption, enhanced lysosomal enzyme release, and markedly increased the procollagenase content of the second pool. The PTH-induced increase in procollagenase was dose dependent and paralleled the extent of calcium loss and lysosomal enzyme release. The increase in procollagenase was found in bone, periosteum, and sutures, where its distribution was similar to that of nonmineralized collagen. The increase in procollagenase was abolished by cycloheximide, but not by indomethacin, hydroxyurea, glucocorticoids, acetazolamide, bisphosphonates, or calcitonin. Calcitonin and bisphosphonates almost completely inhibited the PTH-induced Ca loss and lysosomal enzyme release, but only partially inhibited the PTH-induced loss of collagen. The latter was, however, completely prevented by the collagenase inhibitor, CI-1. CI-1 also partially inhibited the PTH-induced Ca loss. Moreover, collagen degradation occurred in PTH-precultured calvaria (but not in noncultured controls) when incubated in a buffer under nonviable and nondemineralizing conditions. This degradation was inhibited by collagenase inhibitors, either CI-1 or the natural tissue inhibitor of metalloproteinases. This work thus indicates that the resorption of fetal bone explants proceeds along with an accumulation of procollagenase, primarily within their nonmineralized matrix. Moreover the results suggest that collagenase is likely to participate in the degradation of the nonmineralized collagen of the bone explants. Whether it also participates in the degradation of the collagen of the mineralized matrix remains to be elucidated.
通过分析从在各种条件下培养的胎鼠颅骨中提取的前胶原酶，并评估其降解骨胶原的能力，对胶原酶在骨吸收中的作用进行了研究。发现前胶原酶存在于两个不同的池中，一个池提取时需要脱矿质，另一个则不需要。用甲状旁腺激素（PTH）、1,25-二羟基维生素D3、前列腺素E2、白细胞介素-1、肿瘤坏死因子-α、分解代谢素、视黄酸或内毒素（但不用肝素）培养骨骼会诱导骨吸收，增强溶酶体酶释放，并显著增加第二个池中的前胶原酶含量。PTH诱导的前胶原酶增加呈剂量依赖性，与钙流失程度和溶酶体酶释放平行。在前胶原酶增加的情况出现在骨骼、骨膜和缝线中，其分布与非矿化胶原相似。前胶原酶的增加被放线菌酮消除，但消炎痛、羟基脲、糖皮质激素、乙酰唑胺、双膦酸盐或降钙素不能消除。降钙素和双膦酸盐几乎完全抑制PTH诱导的钙流失和溶酶体酶释放，但仅部分抑制PTH诱导的胶原流失。然而，胶原酶抑制剂CI-1可完全阻止后者。CI-1也部分抑制PTH诱导的钙流失。此外，当在无活力和非脱矿质条件下于缓冲液中孵育时，PTH预培养的颅骨（但非未培养的对照）中发生胶原降解。这种降解被胶原酶抑制剂（CI-1或金属蛋白酶的天然组织抑制剂）抑制。因此，这项研究表明，胎骨外植体吸收的同时伴随着前胶原酶的积累，主要在其非矿化基质中。此外，结果表明胶原酶可能参与骨外植体非矿化胶原的降解。它是否也参与矿化基质中胶原的降解仍有待阐明。
