Gao Hongliang, Peng Xing, Li Ning, Gou Liming, Xu Tao, Wang Yuqi, Qin Jian, Liang Hui, Ma Peiqi, Li Shu, Wu Jing, Qin Xihu, Xue Bin
Department of Nephrology, State Key Laboratory of Reproductive Medicine, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
Jiangsu Key Laboratory of Early Development and Chronic Disease Prevention in Children,Nanjing, Jiangsu,PR China.
J Orthop Translat. 2024 Sep 4;48:217-231. doi: 10.1016/j.jot.2024.07.008. eCollection 2024 Sep.
Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone.
Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research).
Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis.
During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases. is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.
对肝骨相互作用的关注度不断提高，激发了人们对各种形式骨质疏松症靶向干预措施的兴趣。不同肝脏疾病引起的肝损伤可导致骨代谢失衡，这表明肝脏与骨骼之间存在一种新的调节模式。然而，肝骨轴在原发性和继发性骨质疏松症中的作用仍未得到充分阐明。因此，探索肝骨轴的确切调节机制可能为治疗肝脏和骨骼相关疾病提供创新的临床方法。
在此，我们通过检索PubMed和Web of Science数据库总结了关于肝骨轴的最新研究，并讨论了肝骨轴在不同类型骨质疏松症中的可能机制。直接报道肝骨轴在不同类型骨质疏松症中调节作用的文献已被纳入本综述的讨论范围（包括但不限于肝骨轴的定义、临床研究和基础研究）。此外，讨论不同病因肝损伤引起骨代谢变化的文章也被纳入本综述的讨论范围（包括但不限于临床研究和基础研究）。
几种内分泌因子（胰岛素样生长因子-1、成纤维细胞生长因子21、铁调素、维生素D、骨钙素、骨桥蛋白、卵磷脂胆固醇酰基转移酶、胎球蛋白-A、前列腺素、骨形态发生蛋白2/9、白细胞介素-1/6/17和肿瘤坏死因子-α）和关键基因（沉默调节蛋白2、ATP结合盒转运蛋白B4、乙醛脱氢酶2、转铁蛋白受体2、血影蛋白β1、锌指蛋白687和固醇调节元件结合蛋白2）可能参与肝骨轴的调节。除了炎症和氧化应激所涉及的经典代谢途径外，肝骨轴介导的铁代谢、胆固醇代谢、脂质代谢和免疫代谢需要更多研究来阐明其在骨质疏松症中的调节机制。
在原发性和继发性骨质疏松症中，肝骨轴通过几种肝细胞因子、骨细胞因子以及生化信号负责肝脏和骨骼的稳态。结合多组学技术和数据挖掘技术可以进一步加深我们对肝骨轴的理解，为管理肝脏和骨骼相关疾病提供新的临床策略。具体如下：肝脏中的代谢异常可能严重影响骨骼的代谢失衡。本综述总结了几种参与肝骨轴的内分泌因子和生化信号通路的不可或缺的作用，并强调了肝脏代谢稳态在骨质疏松症发病机制中的重要作用，这为肝脏和骨骼相关疾病的预防、诊断和治疗提供了新的潜在方向。
