Methionine down‐regulates TLR4/MyD88/NF‐κB signalling in osteoclast precursors to reduce bone loss during osteoporosis

• Published in: British journal of pharmacology Vol. 171; no. 1; pp. 107 - 121
• Main Authors: Vijayan, V, Khandelwal, M, Manglani, K, Gupta, S, Surolia, A
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2014
• Subjects: Acid Phosphatase - metabolism; Administration, Oral; alendronate; Alendronate - pharmacology; Animals; Bone Density - drug effects; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - pharmacology; Bone Remodeling - drug effects; Cells, Cultured; Chemokine CCL3 - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drug Therapy, Combination; Female; Inflammation Mediators - metabolism; Isoenzymes - metabolism; methionine; Methionine - administration & dosage; Methionine - pharmacology; MyD88; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; osteoclast; Osteoclasts - drug effects; Osteoclasts - metabolism; osteoporosis; Osteoporosis - genetics; Osteoporosis - metabolism; Osteoporosis - physiopathology; Osteoporosis - prevention & control; Ovariectomy; RANKL; Rats; Rats, Sprague-Dawley; Research Papers; RNA Interference; Signal Transduction - drug effects; Tartrate-Resistant Acid Phosphatase; Time Factors; Toll-Like Receptor 4 - drug effects; Toll-Like Receptor 4 - metabolism; RANKL; alendronate; osteoclast; osteoporosis; methionine; MyD88
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.12434

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.