ECTS Abstracts (2015) 1 OC1.3

Mechanical loading reduces inflammation-induced human osteocyte-to-osteoclast signalling

Janak L Pathak1,2, Nathalie Bravenboer3, Frank P Luyten2, Patrick Verschueren2, Willem F Lems4, Jenneke Klein-Nulend1 & Astrid D Bakker1


1Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands; 2Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium; 3Department of Clinical Chemistry, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands; 4Department of Rheumatology, MOVE Research Institute Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.


Multiple factors contribute to bone loss in inflammatory diseases such as rheumatoid arthritis (RA), but circulating inflammatory factors and immobilisation play a crucial role. Mechanical loading prevents bone loss in the general population, but the effects of mechanical loading in patients with RA are less clear. Therefore, we aimed to investigate whether mechanical stimuli can reverse the modulatory effects of circulatory inflammatory factors present in RA-serum on osteocyte-to-osteoclast signalling. We also investigated whether inflammatory factors present in RA-serum alter the response of osteocytes to mechanical stimuli. Human primary osteocytes from trabecular bone pieces were treated with 10% serum from active RA patients or healthy controls for 7 days. Then cells were subjected to 1 h mechanical loading by pulsating fluid flow (PFF; 0.7±0.7 Pa, 5 Hz) or static control culture, and medium NO and PGE2 concentrations were determined. Cells were post-incubated without PFF for 1 h, and cytokine gene expression was quantified by qPCR. Osteoclast precursors were cultured for 21 days with PFF-conditioned medium (PFF-CM) or static-conditioned medium (stat-CM) collected after 1 h post-incubation, and osteoclast formation was assessed. RA-serum did not affect IL-6, CYR61, COX2, MEPE, or SOST gene expression in osteocytes. However it enhanced the RANKL/OPG expression ratio by 3.4-fold, while PFF nullified this effect. PFF enhanced NO production in both control-serum and RA-serum-pretreated osteocytes, while PFF only enhanced PGE2 production in control-serum-pretreated osteocytes. Stat-CM from RA-serum-pretreated osteocytes enhanced osteoclastogenesis compared with stat-CM from control-serum-pretreated osteocytes, while PFF-CM from RA-serum-pretreated osteocytes nullified this stimulatory effect on osteoclastogenesis. PFF-CM from control-serum-pretreated osteocytes also inhibited osteoclastogenesis. In conclusion, RA-serum containing inflammatory factors did not alter the intrinsic capacity of osteocytes to sense mechanical stimuli, but induced osteocyte-to-osteoclast communication, while mechanical loading nullified this effect, suggesting that mechanical stimuli could contribute to the prevention of osteoporosis in RA.

Disclosure: The authors declared no competing interests.

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