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Selective β2‐adrenoreceptor signaling regulates osteoclastogenesis via modulating RANKL production and neuropeptides expression in osteocytic MLO‐Y4 cells
Author(s) -
Liang Hengxing,
Zeng Yuanyuan,
Feng Yunzhi,
Wu Hanjiang,
Gong Ping,
Yao Qianqian
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27998
Subject(s) - rankl , osteoprotegerin , endocrinology , medicine , osteoclast , chemistry , receptor , neuropeptide , bone resorption , activator (genetics) , bone remodeling , signal transduction , stimulation , microbiology and biotechnology , biology , biochemistry
The β2‐adrenergic receptor (β2‐AR) signaling on bone cells is the major contributor in the effect of the sympathetic nervous system on bone turnover. However, it remains unclear whether receptor activator of nuclear factor κ‐Β ligand (RANKL) modulation and neuropeptides expression in osteocytes are responsible for the mechanism. This study used β2‐AR stimulation to investigate cell cycle and proliferation, the gene and protein expression of RANKL, and osteoprotegerin (OPG), as well as neuropeptides regulation in osteocytic MLO‐Y4 cells. Clenbuterol (CLE; a β2‐AR agonist) slightly promoted the growth of MLO‐Y4 cells in a concentration‐dependent effect but had no effect on the proliferation index. And the concentration of 10 −8 M showed a significant increase in the S‐phase fraction on day 3 in comparison with the control. Additionally, CLE‐promoted osteoclast formation and bone resorption in osteocytic MLO‐Y4 cell‐RAW264.7 cell cocultures. RANKL expression level and the ratio of RANKL to OPG in MLO‐Y4 cells were enhanced in CLE treatment but were rescued by blocking β2‐AR signaling. However, neuropeptide Y and α‐calcitonin gene‐related peptide, two neurogenic markers, were inhibited in CLE treatment of MLO‐Y4 cells, which was reversed by a β2‐AR blocker. The results indicate that osteocytic β2‐AR plays an important role in the regulation of RANKL/OPG and neuropeptides expression, and β2‐AR signaling in osteocytes can be used as a new valuable target for osteoclast‐related pathologic disease.