2. Academic Validation
  3. Fatty acids derived from apoptotic chondrocytes fuel macrophages FAO through MSR1 for facilitating BMSCs osteogenic differentiation

Fatty acids derived from apoptotic chondrocytes fuel macrophages FAO through MSR1 for facilitating BMSCs osteogenic differentiation

  • Redox Biol. 2022 Jul;53:102326. doi: 10.1016/j.redox.2022.102326.
Zi-Yang Zheng 1,  Tao Jiang 1,  Zhen-Fei Huang 1,  Bo Chu 2,  Jun Gu 3,  Xuan Zhao 1,  Hao Liu 1,  Jin Fan 1,  Li-Peng Yu 1,  Shu-Heng Jiang 4,  Qing Li 4,  Li-Peng Hu 4,  Fan-Qi Kong 5,  Lai Zhang 6,  Qi Chen 6,  Jian Chen 7,  Han-Wen Zhang 8,  Guo-Yong Yin 9,  Shu-Jie Zhao 10
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China; Department of Orthopedics, Xishan People's Hospital of Wuxi City, Wuxi, Jiangsu, 21405, China.
  • 3 Department of Orthopedics, Xishan People's Hospital of Wuxi City, Wuxi, Jiangsu, 21405, China.
  • 4 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 5 Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • 6 Department of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Jiangsu Province on Targeted Intervention of Cardiovascular Diseases, Nanjing, 211166, China.
  • 7 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China. Electronic address: cbccj@sina.com.
  • 8 Department of Pathophysiology, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Jiangsu Province on Targeted Intervention of Cardiovascular Diseases, Nanjing, 211166, China. Electronic address: hanwenzhang@njmu.edu.cn.
  • 9 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China. Electronic address: guoyong_yin@sina.com.
  • 10 Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Institute of Functional Reconstruction and Rehabilitation, Nanjing, Jiangsu, 210029, China. Electronic address: zhaoshujie@njmu.edu.cn.
PMID: 35525025 DOI: 10.1016/j.redox.2022.102326
Abstract

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate Peroxisome Proliferator-activated Receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD+/SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments.

Keywords

Apoptotic chondrocyte; Fatty acid oxidation; MSR1; Macrophage; Osteogenic differentiation.

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