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<p>Cartilaginous endplate (CEP) degeneration is a hallmark feature of intervertebral disc degeneration (IDD) and has been closely linked to the development of low back pain and progressive loss of disc height. Despite its clinical significance, the molecular mechanisms underlying CEP degeneration remain inadequately elucidated. Our study investigated the role of reticulocalbin-2 (RCN2) in CEP cell calcification and inflammation using an in vitro inflammatory model. Gene interference and overexpression experiments demonstrated that RCN2 plays a pivotal role in promoting CEP cell calcification and inflammatory responses by activating the intracellular cAMP/PKA signaling pathway, leading to upregulated expression of calcification-related genes. Further analysis revealed that exosomes secreted by CEP cells contain increased levels of RCN2, which in turn activates the cAMP/PKA signaling pathway and induces calcification in recipient cells. Knockdown of exosomal RCN2 significantly diminished its pro-calcifying effects, thereby establishing RCN2 as a critical mediator. Collectively, these findings elucidate a previously unrecognized molecular mechanism underlying CEP calcification and support RCN2 as a potential therapeutic target for IDD.</p>

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Extracellular reticulocalbin-2 exacerbates cartilage endplate degeneration by promoting calcification via the cAMP/PKA signaling pathway

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Kuijing Han,
  • Han Gao,
  • Wendong Zhang,
  • Wenzhong Zhang,
  • Jijun Huang,
  • Yongxiang Wang

摘要

Cartilaginous endplate (CEP) degeneration is a hallmark feature of intervertebral disc degeneration (IDD) and has been closely linked to the development of low back pain and progressive loss of disc height. Despite its clinical significance, the molecular mechanisms underlying CEP degeneration remain inadequately elucidated. Our study investigated the role of reticulocalbin-2 (RCN2) in CEP cell calcification and inflammation using an in vitro inflammatory model. Gene interference and overexpression experiments demonstrated that RCN2 plays a pivotal role in promoting CEP cell calcification and inflammatory responses by activating the intracellular cAMP/PKA signaling pathway, leading to upregulated expression of calcification-related genes. Further analysis revealed that exosomes secreted by CEP cells contain increased levels of RCN2, which in turn activates the cAMP/PKA signaling pathway and induces calcification in recipient cells. Knockdown of exosomal RCN2 significantly diminished its pro-calcifying effects, thereby establishing RCN2 as a critical mediator. Collectively, these findings elucidate a previously unrecognized molecular mechanism underlying CEP calcification and support RCN2 as a potential therapeutic target for IDD.