IL-6 Alters Osteocyte Signaling toward Osteoblasts but Not Osteoclasts

• Published in: Journal of dental research 2014-04, Vol.93 (4), p.394-399
• Main Authors: Bakker, A.D., Kulkarni, R.N., Klein-Nulend, J., Lems, W.F.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Alkaline phosphatase; Alkaline Phosphatase - drug effects; Animals; Apoptosis; Bone Density - drug effects; Bone marrow; Bone mass; Caspase; Caspase 3 - drug effects; Caspase 7 - drug effects; Caspase-3; Cbfa-1 protein; Cell Communication - drug effects; Cell Culture Techniques; Cell Differentiation - drug effects; Cell Line; Cell Proliferation - drug effects; Communication; Core Binding Factor Alpha 1 Subunit - drug effects; Culture Media, Conditioned; Cytokines; Dentistry; Fluid flow; Gene expression; Gene Expression Regulation - genetics; Interleukin 6; Interleukin-6 - pharmacology; Ki-67 Antigen - drug effects; Mechanical loading; Mechanotransduction, Cellular - drug effects; Mice; Orthodontics; Osteoblastogenesis; Osteoblasts; Osteoblasts - drug effects; Osteocalcin; Osteocalcin - drug effects; Osteoclastogenesis; Osteoclasts; Osteoclasts - drug effects; Osteocytes; Osteocytes - drug effects; Osteoprogenitor cells; Pulsatile Flow - physiology; RANK Ligand - drug effects; Stress, Mechanical; TRANCE protein
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034514522485

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.