Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Bone and Joint Institute, The University of Western Ontario, London, ON N6A 5C1, Canada.
Int J Mol Sci. 2021 Jan 22;22(3):1080. doi: 10.3390/ijms22031080.
Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using knockout mice, this study investigated the role of Panx3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture. Loss of Panx3 did not significantly impact the progression of age-associated histopathological IVD degeneration; however, loss of was associated with decreased gene expression of , , and and altered localization of COLX in the IVD at 19 months-of-age. Following IVD injury in the caudal spine, histological analysis of wild-type mice revealed clusters of hypertrophic cells in the AF associated with increased pericellular proteoglycan accumulation, disruptions in lamellar organization and increased lamellar thickness. In knockout mice, hypertrophic AF cells were rarely detected and AF structure was largely preserved post-injury. Interestingly, uninjured IVDs adjacent to the site of injury more frequently showed evidence of early nucleus pulposus degeneration in knockout mice but remained healthy in wild-type mice. These findings suggest a role for Panx3 in mediating the adaptive cellular responses to altered mechanical stress in the IVD, which may buffer aberrant loads transferred to adjacent motion segments.
连接蛋白 3（Panx3）是一种机械敏感性的、形成通道的糖蛋白，与创伤后骨关节炎的进展有关。尽管有证据表明其在椎间盘（IVD）中有表达，但它在这种软骨关节结构中的功能仍不清楚。本研究使用 Panx3 基因敲除小鼠，研究了 Panx3 在与年龄相关的 IVD 退变和纤维环（AF）针穿刺诱导的退变中的作用。Panx3 的缺失并没有显著影响与年龄相关的组织病理学 IVD 退变的进展；然而，缺失与 、 、 和 的基因表达减少以及 COLX 在 IVD 中的定位改变有关，这些改变发生在 19 月龄时。在尾部脊柱的 IVD 损伤后，对野生型小鼠的组织学分析显示，AF 中存在与细胞外基质蛋白聚糖积累增加、层状结构破坏和层状厚度增加相关的肥大细胞簇。在 Panx3 基因敲除小鼠中，很少检测到肥大的 AF 细胞，损伤后 AF 结构基本保留。有趣的是，未受伤的 IVD 紧邻损伤部位，在 Panx3 基因敲除小鼠中更频繁地出现早期髓核退变的证据，但在野生型小鼠中仍保持健康。这些发现表明 Panx3 在介导细胞对 IVD 中机械应激改变的适应性反应中起作用，这可能缓冲传递到相邻运动节段的异常负荷。
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