Glycosaminoglycans (GAGs) and collagen are the major organic components of bone matrix. However, their roles and functional relationships remain elusive. To investigate the role of GAGs in bone matrix degradation, the effects of GAGs on collagen were examined under acidic conditions that recapitulate the microenvironment of osteoclast resorption pits. We found that sulfated GAGs protect collagen fibrils against acid denaturation. Scanning electron microscopy demonstrated that collagen fibrils retain the fibril structure at pH 4.0 in the presence of chondroitin 6-sulfate. By surface plasmon resonance analysis, we found that sulfated GAGs, but not non-sulfated GAGs, bind to triple-helix type I collagen below pH 4.5. The binding of collagen in an acidic solution was dependent upon the GAG sugar chain length. Functionally, the acid-resistant collagen fibrils generated in the presence of sulfated GAGs were resistant to cathepsin K degradation in vitro below pH 4.0. As the pH increased from 4.0 to 5.0, the acid-resistant collagen fibrils were degraded by cathepsin K. Our results highlight the possibility that the interaction between GAGs and collagen under acidic conditions has a regulatory impact on cathepsin K-mediated bone degradation.

中文翻译：

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糖胺聚糖在组织蛋白酶K降解I型胶原中的新作用

糖胺聚糖（GAG）和胶原蛋白是骨基质的主要有机成分。但是，它们的角色和功能关系仍然难以捉摸。为了研究GAG在骨基质降解中的作用，在概括破骨细胞吸收凹坑微环境的酸性条件下检查了GAG对胶原的影响。我们发现硫酸化的GAGs保护胶原纤维免受酸变性。扫描电子显微镜显示，在6-硫酸软骨素存在下，胶原原纤维在pH 4.0下仍保持原纤维结构。通过表面等离振子共振分析，我们发现硫酸化的GAG而非pH值低于4.5的三螺旋I型胶原与非硫酸化的GAG结合。酸性溶液中胶原蛋白的结合取决于GAG糖链的长度。在功能上 在硫酸盐化的GAG存在下产生的耐酸胶原蛋白原纤维在低于pH 4.0的条件下对组织蛋白酶K降解具有抗性。随着pH从4.0增加到5.0，耐酸性胶原蛋白原纤维被组织蛋白酶K降解。我们的结果表明，酸性条件下GAG与胶原蛋白之间的相互作用可能会对组织蛋白酶K介导的骨降解产生调节作用。