Activation of the Peroxisome Proliferator-Activated Receptor γ Coactivator 1β/NFATc1 Pathway in Circulating Osteoclast Precursors Associated With Bone Destruction in Rheumatoid Arthritis

Arthritis & Rheumatology
Jian-Da MaLie Dai

Abstract

Activation of osteoclastogenesis at the bone site in rheumatoid arthritis (RA) is well established. The mechanisms by which circulating osteoclast precursors contribute are still unclear. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is implicated in transcriptional regulation of osteoclastogenesis in mouse models. This study was undertaken to investigate the contribution of PGC-1β to circulating osteoclast precursors and its link to bone destruction in RA. PGC-1β expression in RA peripheral blood CD14+ monocytes was increased and showed correlation with joint destruction shown on radiographs. Cells from RA patients or healthy controls were transfected with a lentivirus vector for PGC-1β gene silencing or overexpression and cultured with macrophage colony-stimulating factor and RANKL. Bone resorption activity, bone-degrading enzymes, and signaling molecules were measured in these mature osteoclasts. Increased nuclear accumulation of PGC-1β was observed in RA peripheral blood CD14+ monocytes, and these cells had stronger osteoclastogenesis than in healthy controls. PGC-1β protein expression was positively correlated with radiographic joint destruction (r = 0.396-0.413; all P < 0.05). PGC-1β knockdown suppr...Continue Reading

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Citations

Sep 15, 2020·Therapeutic Advances in Musculoskeletal Disease·Jian-Zi LinLie Dai
Apr 20, 2021·Frontiers in Immunology·Yao YaoMeng Zhang
Aug 24, 2021·Journal of Bone and Mineral Metabolism·Haoling ChenFang Huang

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Methods Mentioned

BETA
transfection
immunoprecipitation
electrophoresis
Assay
nuclear translocation

Software Mentioned

ImageJ

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