Initiation of osteoclast bone resorption by interstitial collagenase
Initiation of osteoclast bone resorption by interstitial collagenase
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DOI：
10.1074/jbc.272.35.22053
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发表时间：
1997-08-29
影响因子：
4.8
通讯作者：
Gluck, SL
中科院分区：
文献类型：
--
作者：
Holliday, LS;Welgus, HG;Gluck, SL
破骨细胞在其附着部位形成酸性区室，在该区室中发生骨脱矿和基质降解。虽然半胱氨酸蛋白酶和中性胶原酶都参与骨吸收，但它们的作用仍不清楚。用半胱氨酸蛋白酶抑制剂处理破骨细胞并不影响牙本质切片表面形成的吸收陷窝（“陷窝”）的数量，但它会产生脱矿但充满未降解基质的异常陷窝。用金属蛋白酶抑制剂处理不改变骨陷窝的定性特征，但它大大减少了骨陷窝的数量和吸收的表面积。用抑制性抗大鼠间质胶原酶抗血清处理骨细胞显著减少了骨吸收。在胶原酶抑制剂存在下，用大鼠间质胶原酶预处理牙本质切片或用胶原酶预涂牙本质切片，衍生的明胶肽或热凝胶化胶原。免疫组化显示破骨细胞周围的基质细胞和成骨细胞产生大量的间质胶原酶。这些结果表明间质胶原酶可以作为一种“偶联因子”，通过产生胶原片段激活破骨细胞，从而使成骨细胞启动骨吸收。
Osteoclasts form an acidic compartment at their attachment site in which bone demineralization and matrix degradation occur, Although both the cysteine proteinases and neutral collagenases participate in bone resorption, their roles have remained unclear, Here we show that interstitial collagenase has an essential role in initiating bone resorption, distinct from that of the cysteine proteinases. Treatment of osteoclasts with cysteine proteinase inhibitors did not affect the number of resorption lacunae (''pits'') formed on the surface of dentine slices, but it generated abnormal pits that were demineralized but filled with undegraded matrix. Treatment with metalloproteinase inhibitors did not alter the qualitative features of lacunae, but it greatly reduced the number of pits and surface area resorbed, Treatment of bone cells with an inhibitory anti-rat interstitial collagenase antiserum reduced bone resorption markedly, In the presence of collagenase inhibitors, resorption was restored by pretreatment of dentine slices with rat interstitial collagenase or by precoating the dentine slices with collagenase-derived gelatin peptides or heat-gelatinized collagen. Immunostaining revealed that interstitial collagenase is produced at high levels by stromal cells and osteoblasts adjacent to osteoclasts, These results indicate that interstitial collagenase can function as a ''coupling factor,'' allowing osteoblasts to initiate bone resorption by generating collagen fragments that activate osteoclasts.