Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Int J Mol Sci. 2023 Feb 6;24(4):3179. doi: 10.3390/ijms24043179.
The mechanism of systemic osteoporosis caused by chronic infection is not completely clear, and there is a lack of reasonable interventions for this disease. In this study, heat-killed (HKSA) was applied to simulate the inflammation caused by the typical clinical pathogen and to explore the mechanism of systemic bone loss caused by it. In this study, we found that the systemic application of HKSA caused bone loss in mice. Further exploration found that HKSA caused cellular senescence, telomere length shortening, and telomere dysfunction-induced foci (TIF) in limb bones. As a well-known telomerase activator, cycloastragenol (CAG) significantly alleviated HKSA-induced telomere erosion and bone loss. These results suggested that telomere erosion in bone marrow cells is a possible mechanism of HKSA-induced bone loss. CAG may protect against HKSA-induced bone loss by alleviating telomere erosion in bone marrow cells.
慢性感染导致全身性骨质疏松症的机制尚不完全清楚,针对这种疾病缺乏合理的干预措施。在本研究中,应用热灭活金黄色葡萄球菌(HKSA)模拟典型临床病原体引起的炎症,以探讨其导致全身性骨丢失的机制。本研究发现,全身性应用 HKSA 可导致小鼠骨丢失。进一步的探索发现,HKSA 导致肢体骨骼中的细胞衰老、端粒长度缩短和端粒功能障碍诱导的焦点(TIF)。环黄芪醇(CAG)作为一种众所周知的端粒酶激活剂,可显著减轻 HKSA 诱导的端粒侵蚀和骨丢失。这些结果表明,骨髓细胞中端粒侵蚀可能是 HKSA 诱导骨丢失的一种机制。CAG 可能通过减轻骨髓细胞中端粒侵蚀来预防 HKSA 诱导的骨丢失。