{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:31:08Z","timestamp":1791095468720,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2009,10,29]],"date-time":"2009-10-29T00:00:00Z","timestamp":1256774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Research Institute MOVE of the Vrije Universiteit Amsterdam"},{"name":"Foundation for the Coordination of Higher Education and Graduate Training, Brazil","award":["MEC\/CAPES BEX0481\/06-8"],"award-info":[{"award-number":["MEC\/CAPES BEX0481\/06-8"]}]},{"name":"Space Research Organization of The Netherlands","award":["MG-055"],"award-info":[{"award-number":["MG-055"]}]},{"DOI":"10.13039\/501100001718","name":"Netherlands Organization For International Cooperation In Higher Education","doi-asserted-by":"crossref","award":["Physics Development Project grant PHL-146"],"award-info":[{"award-number":["Physics Development Project grant PHL-146"]}],"id":[{"id":"10.13039\/501100001718","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Inflammatory diseases often coincide with reduced bone mass. Mechanoresponsive osteocytes regulate bone mass by maintaining the balance between bone formation and resorption. Despite its biologic significance, the effect of inflammation on osteocyte mechanoresponsiveness is not understood. To fill this gap, we investigated whether the inflammatory cytokines tumor necrosis factor \u03b1 (TNF\u03b1) and interleukin\u20101\u03b2 (IL\u20101\u03b2) modulate the osteocyte response to mechanical loading.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MLO\u2010Y4 osteocytes were incubated with TNF\u03b1 (0.5\u201330 ng\/ml) or IL\u20101\u03b2 (0.1\u201310 ng\/ml) for 30 minutes or 24 hours, or with calcium inhibitors for 30 minutes. Cells were subjected to mechanical loading by pulsatile fluid flow (mean \u00b1 amplitude 0.7 \u00b1 0.3 Pa, 5 Hz), and the response was quantified by measuring nitric oxide (NO) production using Griess reagent and by measuring intracellular calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) using Fluo\u20104\/AM. Focal adhesions and filamentous actin (F\u2010actin) were visualized by immunostaining, and apoptosis was quantified by measuring caspase 3\/7 activity. Cell\u2010generated tractions were quantified using traction force microscopy, and cytoskeletal stiffness was quantified using optical magnetic twisting cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pulsatile fluid flow increased [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>within seconds (in 13% of cells) and NO production within 5 minutes (4.7\u2010fold). TNF\u03b1 and IL\u20101\u03b2 inhibited these responses. Calcium inhibitors decreased pulsatile fluid flow\u2013induced NO production. TNF\u03b1 and IL\u20101\u03b2 affected cytoskeletal stiffness, likely because 24 hours of incubation with TNF\u03b1 and IL\u20101\u03b2 decreased the amount of F\u2010actin. Incubation with IL\u20101\u03b2 for 24 hours stimulated osteocyte apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that TNF\u03b1 and IL\u20101\u03b2 inhibit mechanical loading\u2013induced NO production by osteocytes via abrogation of pulsatile fluid flow\u2013stimulated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, and that IL\u20101\u03b2 stimulates osteocyte apoptosis. Since both NO and osteocyte apoptosis affect osteoclasts, these findings provide a mechanism by which inflammatory cytokines might contribute to bone loss and consequently affect bone mass in rheumatoid arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24920","type":"journal-article","created":{"date-parts":[[2009,10,29]],"date-time":"2009-10-29T21:16:37Z","timestamp":1256850997000},"page":"3336-3345","source":"Crossref","is-referenced-by-count":85,"title":["Tumor necrosis factor \u03b1 and interleukin\u20101\u03b2 modulate calcium and nitric oxide signaling in mechanically stimulated osteocytes"],"prefix":"10.1002","volume":"60","author":[{"given":"A. D.","family":"Bakker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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