IL-6 alters osteocyte signaling toward osteoblasts but not osteoclasts

Mechanosensitive osteocytes regulate bone mass in adults. interleukin 6 (il-6),such as present during orthodontic tooth movement,also strongly affects bone mass,but little is known about the effect of il-6 on osteocyte function. therefore we aimed to determine in vitro whether il-6 affects osteocyte mechanosensitivity,and osteocyte regulation of osteoclastogenesis and osteoblast differentiation. mlo-y4 osteocytes were incubated with/without il-6 (1 or 10 pg/ml) for 24 hr. subsequently,osteocytes were subjected to mechanical loading by pulsating fluid flow (pff) for 1 hr. mouse osteoclast precursors were cultured for 7 days on top of il-6-treated osteocytes. conditioned medium from osteocytes treated with/without il-6 was added to mc3t3-e1 pre-osteoblasts for 14 days. exogenous il-6 (10 pg/ml) did not alter the osteocyte response to pff. pff significantly enhanced il-6 production by osteocytes. il-6 enhanced rankl expression but reduced caspase 3/7 activity by osteocytes,and therefore did not affect osteocyte-stimulated osteoclastogenesis. conditioned medium from il-6-treated osteocytes reduced alkaline phosphatase (alp) activity and runx2 expression in osteoblasts,but increased expression of the proliferation marker ki67 and osteocalcin. our results suggest that il-6 is produced by shear-loaded osteocytes and that il-6 may affect bone mass by modulating osteocyte communication toward osteoblasts. © international & american associations for dental research.