caa a22 4500 605520976 CHVBK 20210128100738.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00223-015-9999-z doi (NATIONALLICENCE)springer-10.1007/s00223-015-9999-z Mechanical Loading Reduces Inflammation-Induced Human Osteocyte-to-Osteoclast Communication [Elektronische Daten] [Janak Pathak, N. Bravenboer, Frank Luyten, Patrick Verschueren, Willem Lems, Jenneke Klein-Nulend, Astrid Bakker] Multiple factors contribute to bone loss in inflammatory diseases such as rheumatoid arthritis (RA), but circulating inflammatory factors and immobilization 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 reverse the stimulatory effect of RA serum on osteocyte-to-osteoclast communication. Human primary osteocytes were pretreated with 10% RA serum or healthy control serum for 7days, followed by 1h±mechanical loading by pulsating fluid flow (PFF). Nitric oxide (NO) and prostaglandin E2 were measured in the medium. Receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-6 (IL-6), cyclooxygenase-2 (COX2), matrix-extracellular phosphoglycoprotein (MEPE), cysteine-rich protein 61 (CYR61), and SOST gene expression was quantified by qPCR. Osteoclast precursors were cultured with PFF-conditioned medium (PFF-CM) or static-conditioned medium (stat-CM), and osteoclast formation was assessed. RA serum alone did not affect IL-6, CYR61, COX2, MEPE, or SOST gene expression in osteocytes. However, RA serum enhanced the RANKL/OPG expression ratio by 3.4-fold, while PFF nullified this effect. PFF enhanced NO production to the same extent in control serum (2.6-3.5-fold) and RA serum-pretreated (2.7-3.6-fold) osteocytes. Stat-CM from RA serum-pretreated osteocytes enhanced osteoclastogenesis compared with stat-CM from control serum-pretreated osteocytes, while PFF nullified this effect. In conclusion, RA serum, containing inflammatory factors, did not alter the intrinsic capacity of osteocytes to sense mechanical stimuli, but upregulated osteocyte-to-osteoclast communication. Mechanical loading nullified this upregulation, suggesting that mechanical stimuli could contribute to the prevention of osteoporosis in inflammatory disease. The Author(s), 2015 Rheumatoid arthritis nationallicence Generalized osteoporosis nationallicence Inflammatory cytokines nationallicence Pulsating fluid flow nationallicence Osteoclastogenesis nationallicence Pathak Janak Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut Bravenboer N. Department of Clinical Chemistry, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut Luyten Frank Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium aut Verschueren Patrick Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium aut Lems Willem Department of Rheumatology, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut Klein-Nulend Jenneke Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut Bakker Astrid Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/2(2015-08-01), 169-178 0171-967X 97:2<169 2015 97 223 https://doi.org/10.1007/s00223-015-9999-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-9999-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pathak Janak Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Bravenboer N. Department of Clinical Chemistry, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Luyten Frank Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Verschueren Patrick Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Lems Willem Department of Rheumatology, VU University Medical Center, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Klein-Nulend Jenneke Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Bakker Astrid Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/2(2015-08-01), 169-178 0171-967X 97:2<169 2015 97 223