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Methionine, a sulphur\u2010containing 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The anti\u2010resorptive effect of methionine, (250\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized (<jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>) rats by monitoring changes in bone turnover, formation of osteoclasts from blood\u2010derived mononuclear cells and changes in the synthesis of pro\u2010osteoclastogenic cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>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\u20101\u03b1. siRNA\u2010mediated knockdown of myeloid differentiation primary response 88 [MyD88], a signalling molecule in the toll\u2010like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP\u20101\u03b1 in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR\u20104\/MyD88\/NF\u2010\u03baB pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>TLR\u20104\/MyD88\/NF\u2010\u03baB signalling pathway is integral for osteoclast development and this is down\u2010regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12434","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:30:05Z","timestamp":1381541405000},"page":"107-121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Methionine down\u2010regulates <scp>TLR<\/scp>4\/<scp>MyD<\/scp>88\/<scp>NF<\/scp>\u2010\u03ba<scp>B<\/scp> signalling in osteoclast precursors to reduce bone loss during osteoporosis"],"prefix":"10.1111","volume":"171","author":[{"given":"V","family":"Vijayan","sequence":"first","affiliation":[{"name":"Molecular Sciences Laboratory National Institute of Immunology  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Khandelwal","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit Indian Institute of Science  Bangalore 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