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- Title
Complement C1q production by osteoclasts and its regulation of osteoclast development.
- Authors
TEO, Boon Heng Dennis; BOBRYSHEV, Yuri V.; TEH, Boon King; WONG, Siew Heng; LU, Jinhua
- Abstract
C1q deficiency is the strongest known risk factor for SLE (systemic lupus erythematosus) but its endogenous cellular origin remains limitedly understood. In the present study we investigate the production of C1q by both cultured and endogenous bone osteoclasts. Blood monocytes were cultured with RANKL (receptor activator of nuclear factor ?B ligand) and M-CSF (macrophage colony-stimulating factor) to generate osteoclasts and these cells expressed C1Q mRNA and also secreted C1q protein. Intracellular C1q was detectable in developing osteoclasts at day 3 by Western blotting and was also detectable by flow cytometry. By immunofluorescence microscopy, C1q was preferentially detected in immature osteoclasts. By multiple detection methods, C1q expression was markedly increased after IFN? (interferon ? ) treatment. By immunohistochemistry, C1q was also detected in endogenous bone osteoclasts. When osteoclasts were cultured on immobilized C1q, these cells exhibited 2-7-fold increases in the expression of signature osteoclast genes [TRAP (tartrate-resistant acid phosphatase), cathepsin K, calcitonin receptor, carbonic anhydrase II and NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1)], suggesting an osteoclastogenic capability. This is the first report of C1q production by osteoclasts. Its ability to enhance osteoclast development implies reduced osteoclastogenesis in patients with SLE as they often experience decreased C1q levels. This is consistent with the non-erosive nature of lupus arthritis.
- Subjects
OSTEOCLASTS; SYSTEMIC lupus erythematosus; MESSENGER RNA; IMMUNOFLUORESCENCE; FLOW cytometry; DENDRITIC cells; LUPUS erythematosus; DISEASE risk factors
- Publication
Biochemical Journal, 2012, Vol 447, Issue 2, p229
- ISSN
0264-6021
- Publication type
Article
- DOI
10.1042/BJ20120888