Ctahepsin K degrades osteoprotegerin to promote osteoclastogenesis in vitro.
Ctahepsin K degrades osteoprotegerin to promote osteoclastogenesis in vitro.
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Ctahepsin K 降解骨保护素以促进体外破骨细胞生成。
DOI：
10.1007/s11626-023-00747-5
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Kamijo R
中科院分区：
文献类型：
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作者：
Kawai R;Sugisaki R;Miyamoto Y;Yano F;Sasa K;Minami E;Maki K;Kamijo R
成骨细胞产生核因子-κ B配体受体激活因子（RANKL）和骨保护素（osteoprotegerin），它们是破骨细胞分化和活化的诱导剂和抑制剂。我们先前提出牙龈卟啉单胞菌的赖氨酸特异性牙龈蛋白酶和中性粒细胞弹性蛋白酶降解骨保护素是与感染和炎症相关的骨吸收机制之一。在本研究中，我们发现，组织蛋白酶K（CTSK）也降解护骨素在酸性环境和缓冲液的pH值为7.4。通过与CTSK反应产生的骨保护素的37 k片段根据反应时间进一步降解成低分子量片段，包括13 k片段。37 k片段的N-末端氨基酸序列与完整的骨保护素的序列相匹配，表明CTSK优先水解骨保护素的死亡结构域样区域，而不是其RANKL结合区域。骨保护素的13 k片段是37 k片段RANKL结合区内的C-末端13 k部分。最后，CTSK恢复RANKL依赖的破骨细胞分化，这是由加入骨保护素抑制。总的来说，CTSK可能是破骨细胞生成的正调节因子。
Osteoblasts produce the receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin, the inducer and the suppressor of osteoclast differentiation and activation. We previously proposed that the degradation of osteoprotegerin by lysine-specific gingipain ofPorphyromonas gingivalisand neutrophil elastase is one of the mechanisms of bone resorption associated with infection and inflammation. In the present study, we found that cathepsin K (CTSK) also degraded osteoprotegerin in an acidic milieu and the buffer with a pH of 7.4. The 37 k fragment of osteoprotegerin produced by the reaction with CTSK was further degraded into low molecular weight fragments, including a 13 k fragment, depending on the reaction time. TheN-terminal amino acid sequence of the 37 k fragment matched that of the intact osteoprotegerin, indicating that CTSK preferentially hydrolyzes the death domain-like region of osteoprotegerin, not its RANKL-binding region. The 13 k fragment of osteoprotegerin was the C-terminal 13 k portion within the RANKL-binding region of the 37 k fragment. Finally, CTSK restored RANKL-dependent osteoclast differentiation that was suppressed by the addition of osteoprotegerin. Collectively, CTSK is a possible positive regulator of osteoclastogenesis.