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<p>Osteoarthritis (OA) is a leading cause of disability among the elderly, characterized by aberrant subchondral bone remodeling that precedes cartilage degeneration. We identify parvalbumin (Pvalb) in osteocytes as a critical mechanosensory regulator of this pathological process. Pvalb expression is significantly reduced in osteocytes from both OA patients and male murine models of the disease. Conditional deletion of Pvalb in osteocytes accelerates OA progression, whereas bone-targeted restoration of Pvalb expression mitigates disease manifestations. Mechanistically, Pvalb maintains calcium homeostasis by competing with CaMKIV for calmodulin binding. Under excessive mechanical loading, Pvalb expression is suppressed, leading to activation of the Ca²<sup>+</sup>-CaMKIV-CREB signaling pathway, increased RANKL production, and subsequent osteoclast activation and pathological bone remodeling. These findings identifies an osteocyte-mediated mechanotransduction pathway in OA pathogenesis and underscore Pvalb as a promising therapeutic target.</p>

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Osteocyte parvalbumin mediates mechanotransduction to attenuate osteoarthritis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月14日

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  • Jiansen Su,
  • Chuan Li,
  • Yiwei Chen,
  • Yiwei Hu,
  • Lanlan Wang,
  • Qian Tang,
  • Changqing Zhang,
  • Junhui Yin

摘要

Osteoarthritis (OA) is a leading cause of disability among the elderly, characterized by aberrant subchondral bone remodeling that precedes cartilage degeneration. We identify parvalbumin (Pvalb) in osteocytes as a critical mechanosensory regulator of this pathological process. Pvalb expression is significantly reduced in osteocytes from both OA patients and male murine models of the disease. Conditional deletion of Pvalb in osteocytes accelerates OA progression, whereas bone-targeted restoration of Pvalb expression mitigates disease manifestations. Mechanistically, Pvalb maintains calcium homeostasis by competing with CaMKIV for calmodulin binding. Under excessive mechanical loading, Pvalb expression is suppressed, leading to activation of the Ca²+-CaMKIV-CREB signaling pathway, increased RANKL production, and subsequent osteoclast activation and pathological bone remodeling. These findings identifies an osteocyte-mediated mechanotransduction pathway in OA pathogenesis and underscore Pvalb as a promising therapeutic target.