Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus spread by the Aedes species of mosquito. Chikungunya virus causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal the presence of bone lesions and erosive arthritis in the joints of CHIKV-infected patients, indicating an association of bone pathology with CHIKV infection. However, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Bone marrow-derived mesenchymal stem cells (BMSCs) contribute to bone homeostasis by differentiating into osteogenic cells which later mature to form the bone. Disruption of osteogenic differentiation and function of BMSCs leads to bone pathologies. Studies show that virus infections can alter the properties and function of BMSCs. However, to date, pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMSCs and osteogenic cells to CHIKV and studied the effect of infection on these cells. For the first time to our knowledge, we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed decreased gene expression of the major regulator of osteogenic differentiation, RUNX2, in CHIKV-infected osteogenic cells. Furthermore, impaired functional properties of osteogenic cells, i.e., decreased production and activity of alkaline phosphatase (ALP) and matrix mineralization, were observed in the presence of CHIKV infection. Thus, we conclude that CHIKV likely impairs osteogenic differentiation of BMSCs, indicating a possible role of BMSCs in altering bone homeostasis during CHIKV infection.

中文翻译：

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基孔肯雅病毒感染损害成骨细胞的功能。

基孔肯雅病毒 (CHIKV) 是一种由伊蚊传播的正链单链 RNA 病毒蚊子的种类。基孔肯雅热病毒会导致以高烧、头痛、皮疹和关节痛为特征的病症。最近的研究表明，CHIKV 感染患者的关节中存在骨病变和侵蚀性关节炎，表明骨病理与 CHIKV 感染有关。然而，CHIKV 诱导的骨病理学的分子机制仍不清楚。骨髓来源的间充质干细胞 (BMSCs) 通过分化成成骨细胞，然后成熟形成骨来促进骨稳态。BMSCs 的成骨分化和功能的破坏导致骨病变。研究表明，病毒感染可以改变 BMSCs 的特性和功能。然而，迄今为止，尚未研究在这种情况下 CHIKV 感染的发病机制。在目前的研究中，我们研究了 BMSCs 和成骨细胞对 CHIKV 的敏感性，并研究了感染对这些细胞的影响。据我们所知，我们第一次报告 CHIKV 可以有效地感染 BMSCs 和成骨细胞。我们还观察到 CHIKV 感染的成骨细胞中成骨分化的主要调节因子 RUNX2 的基因表达降低。此外，在 CHIKV 感染的情况下，观察到成骨细胞的功能特性受损，即碱性磷酸酶 (ALP) 和基质矿化的产生和活性降低。因此，我们得出结论，CHIKV 可能会损害 BMSC 的成骨分化，表明 BMSC 在 CHIKV 感染期间可能在改变骨稳态方面发挥作用。