Department of Orthopedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou 325000, China.
Oxid Med Cell Longev. 2022 Aug 17;2022:5098358. doi: 10.1155/2022/5098358. eCollection 2022.
Bone metabolism occurs in the entire life of an individual and is required for maintaining skeletal homeostasis. The imbalance between osteogenesis and osteoclastogenesis eventually leads to osteoporosis. Oxidative stress is considered a major cause of bone homeostasis disorder, and relieving excessive oxidative stress in bone mesenchymal stem cells (BMSCs) is a potential treatment strategy for osteoporosis. Carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide (CO), possesses antioxidation, antiapoptosis, and anti-inflammatory properties. In our study, we found that CORM-3 could reduce reactive oxygen species (ROS) accumulation and prevent mitochondrial dysfunction thereby restoring the osteogenic potential of the BMSCs disrupted by hydrogen peroxide (HO) exposure. The action of CORM-3 was preliminarily considered the consequence of Nrf2/HO-1 axis activation. In addition, CORM-3 inhibited osteoclast formation in mouse primary bone marrow monocytes (BMMs) by inhibiting HO-induced polarization of M1 macrophages and endowing macrophages with M2 polarizating ability. Rat models further demonstrated that CORM-3 treatment could restore bone mass and enhance the expression of Nrf2 and osteogenic markers in the distal femurs. In summary, CORM-3 is a potential therapeutic agent for the treatment of osteoporosis.
骨骼代谢发生在个体的整个生命周期中，是维持骨骼内稳态所必需的。成骨作用和破骨细胞形成作用之间的失衡最终会导致骨质疏松症。氧化应激被认为是骨内稳态紊乱的主要原因，缓解骨髓间充质干细胞（BMSCs）中过度的氧化应激是骨质疏松症的一种潜在治疗策略。一氧化碳释放分子-3（CORM-3）作为一氧化碳（CO）的经典供体，具有抗氧化、抗凋亡和抗炎作用。在我们的研究中，我们发现 CORM-3 可以减少活性氧（ROS）的积累，防止线粒体功能障碍，从而恢复因过氧化氢（HO）暴露而受损的 BMSCs 的成骨潜能。CORM-3 的作用初步被认为是 Nrf2/HO-1 轴激活的结果。此外，CORM-3 通过抑制 HO 诱导的 M1 巨噬细胞极化，并赋予巨噬细胞 M2 极化能力，抑制了小鼠原代骨髓单核细胞（BMMs）中的破骨细胞形成。大鼠模型进一步表明，CORM-3 治疗可恢复骨量并增强远端股骨中 Nrf2 和成骨标志物的表达。综上所述，CORM-3 是治疗骨质疏松症的一种潜在治疗剂。
