TY - JOUR AB - The treatment of osteoporosis typically inhibits the activity of osteoclasts, which subsequently results in the suppression of bone formation and maintenance, however the underlying mechanism remains to be elucidated. The receptor activator of nuclear factor κ‑B ligand (RANKL)‑receptor activator of nuclear factor κ‑B (RANK) signaling axis is important in the osteoblast regulation of osteoclasts. RANKL surface‑bound molecules expressed on T cells stimulate a reverse signaling transduction in order to regulate the T cells, therefore the present study hypothesized that RANKL expressed on osteoblasts may transfer reverse signals to regulate osteoblasts. A series of experiments were designed to test the hypothesis, using MTT, stealth RNA interference, reverse transcription‑quantitative polymerase chain reaction, western blot analysis, alkaline phosphatase activity assay and alizarin red staining. The present study observed the role of RANK‑RANKL reverse signaling on osteoblasts, regulated by osteoclasts. Osteoblasts were treated with recombinant RANK proteins. The soluble RANK enhanced the mineralization of osteoblasts. When the RANKL was knocked down in the osteoblast, RANK demonstrated a weak osteogenic effect on the RANKL‑deficient osteoblast compared with the wild‑type osteoblast which served as a control. Addition of soluble RANK activated the p38 mitogen activated protein kinase (MAPK) signaling pathway in the osteoblast and blocking this same pathway in E1 cells reduced the effect of RANK. In the co‑culture system of osteoblasts and osteoclasts, p38 MAPK in E1 cells was phosphorylated a short time following co‑culture and the phosphorylation then blocked by abundant soluble RANKL. The findings suggested that RANKL expressed on osteoblasts transferred reverse signals from the exterior of the cell to the interior, which regulated the osteoblasts. AD - Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China AU - Zhang,Shiqian AU - Wang,Xiaoyu AU - Li,Guojun AU - Chong,Yang AU - Zhang,Jie AU - Guo,Xinzhen AU - Li,Baoxin AU - Bi,Zhenggang DA - 2017/10/01 DO - 10.3892/mmr.2017.7039 EP - 4000 IS - 4 JO - Mol Med Rep KW - osteoporosis receptor activator of nuclear factor κ‑B ligand‑receptor activator of nuclear factor κ‑B osteoclast osteoblast reverse signal PY - 2017 SN - 1791-2997 1791-3004 SP - 3994 ST - Osteoclast regulation of osteoblasts via RANK‑RANKL reverse signal transduction in vitro T2 - Molecular Medicine Reports TI - Osteoclast regulation of osteoblasts via RANK‑RANKL reverse signal transduction in vitro UR - https://doi.org/10.3892/mmr.2017.7039 VL - 16 ER -