BONE-RESORBING AGENTS AFFECT THE PRODUCTION AND DISTRIBUTION OF PROCOLLAGENASE AS WELL AS THE ACTIVITY OF COLLAGENASE IN BONE TISSUE
BONE-RESORBING AGENTS AFFECT THE PRODUCTION AND DISTRIBUTION OF PROCOLLAGENASE AS WELL AS THE ACTIVITY OF COLLAGENASE IN BONE TISSUE
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DOI：
10.1210/endo-123-1-264
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发表时间：
1988-07-01
期刊：
影响因子：
4.8
通讯作者：
VAES, G
中科院分区：
文献类型：
--
作者：
DELAISSE, JM;EECKHOUT, Y;VAES, G
胶原酶在骨吸收中的参与已经通过测定从在各种条件下培养的胎鼠颅盖骨中提取的胶原酶原，并通过评估其降解骨胶原的能力来研究。在两个单独的池中发现了胶原酶原，一个需要脱矿以进行提取，另一个不需要。用PTH、1，25-二羟维生素D3、前列腺素E2、白细胞介素-1、肿瘤坏死因子-α培养骨，分解代谢素、视黄酸或内毒素（但不含肝素）诱导再吸收，增强溶酶体酶释放，并显著增加第二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，并与钙丢失和溶酶体酶释放的程度相关。在骨、骨膜和骨缝中发现前胶原酶的增加，其分布与非矿化胶原相似。放线菌酮可消除前胶原酶的增加，但吲哚美辛、羟基脲、糖皮质激素、乙酰唑胺、双膦酸盐或降钙素不能消除前胶原酶的增加。降钙素和二磷酸盐几乎完全抑制PTH诱导的Ca丢失和溶酶体酶释放，但仅部分抑制PTH诱导的胶原丢失。然而，后者完全被胶原酶抑制剂CI-1所阻止。CI-1还部分抑制PTH诱导的Ca丢失。此外，胶原蛋白降解发生在PTH预培养的颅骨（但不是在非培养的控制）时，在缓冲液中孵育的nonviable和nondemineralizing条件下。胶原酶抑制剂，CI-1或金属蛋白酶的天然组织抑制剂抑制这种降解。因此，这项工作表明，胎儿骨外植体的吸收进行沿着胶原原酶的积累，主要是在其非矿化基质。胶原酶可能参与了骨移植物中非矿化胶原的降解。它是否也参与矿化基质胶原的降解仍有待阐明。
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 procallagenase 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.