Department of Orthopedics, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024 Aug 25;53(4):427-433. doi: 10.3724/zdxbyxb-2023-0615.
Segmental bone defects and nonunion of fractures caused by trauma, infection, tumor or systemic diseases with limited osteogenesis and prolonged bone healing cycles are challenging issues in orthopedic clinical practice. Therefore, identifying regulatory factors for bone tissue regeneration and metabolism is crucial for accelerating bone repair and reconstructing defective areas. Silence information regulator 6 (SIRT6), functioning as a deacetylase and nucleotide transferase, is extensively involved in the regulation of differentiation, apoptosis, metabolism, and inflammation in bone cells including osteoblasts and osteoclasts, and is considered to be an important factor in regulating bone metabolism. SIRT6 forms a complex with B lymphocyte-induced maturation protein 1 (Blimp1), down-regulates the expression of the nuclear factor κB (NF-κB) pathway, and promotes the expression of the ERα-FasL axis signal to inhibit osteoclast formation and maturation differentiation, thereby hindering bone resorption and increasing bone mass. In addition, SIRT6 activates the Akt-mTOR pathway to regulate the autophagy level and osteogenesis of bone marrow mesenchymal stem cells, inhibits glycolysis and reactive oxygen production in osteoblasts, promotes osteoblast differentiation through the CREB/CCN1/COX2 pathway and the bone morphogenetic protein (BMP) signaling pathway, enhances bone formation, and accelerates bone regeneration and repair of skeletal tissue. This article provides an overview of the research progress on SIRT6 in the pathophysiology of bone regeneration, revealing its potential as a novel therapeutic target for bone tissue repair to alleviate the progression of skeletal pathological diseases.
节段性骨缺损和骨折不愈合是创伤、感染、肿瘤或全身性疾病引起的，这些疾病的成骨有限，骨愈合周期延长，是骨科临床实践中的难题。因此，确定骨组织再生和代谢的调节因子对于加速骨修复和重建缺损区域至关重要。沉默信息调节因子 6（SIRT6）作为一种去乙酰化酶和核苷酸转移酶，广泛参与成骨细胞和破骨细胞分化、凋亡、代谢和炎症的调节，被认为是调节骨代谢的重要因素。SIRT6 与 B 淋巴细胞诱导成熟蛋白 1（Blimp1）形成复合物，下调核因子 κB（NF-κB）通路的表达，促进 ERα-FasL 轴信号的表达，抑制破骨细胞的形成和成熟分化，从而抑制骨吸收，增加骨量。此外，SIRT6 激活 Akt-mTOR 通路来调节骨髓间充质干细胞的自噬水平和成骨作用，抑制成骨细胞中的糖酵解和活性氧的产生，通过 CREB/CCN1/COX2 通路和骨形态发生蛋白（BMP）信号通路促进成骨细胞分化，增强骨形成，加速骨骼组织的再生和修复。本文综述了 SIRT6 在骨再生病理生理学中的研究进展，揭示了其作为骨组织修复的新型治疗靶点的潜力，以缓解骨骼病理疾病的进展。
