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Methionine down‐regulates TLR 4/ MyD 88/ NF ‐κ B signalling in osteoclast precursors to reduce bone loss during osteoporosis
Author(s) -
Vijayan V,
Khandelwal M,
Manglani K,
Gupta S,
Surolia A
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12434
Subject(s) - osteoclast , methionine , rankl , chemistry , ovariectomized rat , osteoporosis , bone resorption , endocrinology , medicine , osteoblast , bone remodeling , receptor , biochemistry , amino acid , hormone , activator (genetics) , in vitro
Background and Purpose Studies have demonstrated that a moderate intake of amino acids is associated with development of bone health. Methionine, a sulphur‐containing essential amino acid, has been largely implicated for improving cartilage formation, however its physiological significance on bone integrity and functionality have not been elucidated. We investigated whether methionine can prevent osteoporotic bone loss. Experimental Approach The anti‐resorptive effect of methionine, (250 mg kg −1 body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized ( OVX ) rats by monitoring changes in bone turnover, formation of osteoclasts from blood‐derived mononuclear cells and changes in the synthesis of pro‐osteoclastogenic cytokines. Key results Methionine improved bone density and significantly decreased the degree of osteoclast development from blood mononuclear cells in OVX rats, as indicated by decreased production of osteoclast markers tartarate resistant acid phosphatase b (TRAP5b) and MIP‐1α. siRNA‐mediated knockdown of myeloid differentiation primary response 88 [MyD88], a signalling molecule in the toll‐like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP‐1α in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR‐4/MyD88/NF‐κB pathway. Conclusions and Implications TLR‐4/MyD88/NF‐κB signalling pathway is integral for osteoclast development and this is down‐regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis.