• Dechun Chen, Yu Chen, Tiefeng Li, Lei Shi, Mengxiao Pan, and Deyu Chen.
• Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
• Spine. 2017 Dec 1; 42 (23): E1334-E1341.

Study DesignIn vivo and in vitro experiments.ObjectiveTo illustrate the further molecular mechanism of Cx43-mediated osteoblastic differentiation of ligament cells.Summary Of Background DataOssification of the posterior longitudinal ligament (OPLL) is one of the main causes of myelopathy in Asians, but its etiology has not been clarified. We have previously found the mechanical stress can upregulate Cx43 expression in ligament cells, which transduces mechanical signal to promote osteoblastic differentiation.MethodsThe posterior longitudinal ligaments were collected intraoperatively. Ligament fibroblasts were isolated and cultured, and an in vitro mechanical loading model was established. In vivo and in vitro expression levels of Cx43 protein were compared between OPLL and non-OPLL patients. The activation of nuclear factor (NF)-κB (p65) signal and related inflammatory responses were detected in ligament cells under mechanical loading. The mechanical stress-induced inflammatory response and osteoblastic differentiation of OPLL cells were investigated after the treatment with Cx43 siRNA or NFкB (p65) inhibitor.ResultsWe first confirmed higher Cx43 levels in both in vivo ligament tissue from OPLL patients and in vitro cultured OPLL cells. We also found NFκB (p65) signal and related inflammatory response were activated by mechanical stimulation. The activation of NFκB (p65) signal was dependent upon Cx43, as its knockdown reduced signal. Moreover, treatment with Cx43 siRNA or NFкB (p65) inhibitor significantly decreased the mechanical-induced inflammation response, but partly attenuated mechanical-stimulated osteoblastic differentiation of OPLL cells.ConclusionCx43-mediated NFкB (p65) signal played an important role in mechanical stress-induced OPLL by transduction of mechanical signal, while giving rise to the activation of inflammatory response in ligament fibroblastsLevel of Evidence: N/A.

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