Methionine down-regulates TLR4/MyD88/NF-kappa B signalling in osteoclast precursors to reduce bone loss during osteoporosis

Vijayan, V and Khandelwal, M and Manglani, K and Gupta, S and Surolia, A (2014) Methionine down-regulates TLR4/MyD88/NF-kappa B signalling in osteoclast precursors to reduce bone loss during osteoporosis. In: BRITISH JOURNAL OF PHARMACOLOGY, 171 (1). pp. 107-121.

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Abstract

Background and PurposeStudies 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 ApproachThe anti-resorptive effect of methionine, (250mgkg(-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 resultsMethionine 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-1. 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-1 in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR-4/MyD88/NF-B pathway. Conclusions and ImplicationsTLR-4/MyD88/NF-B 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.

Item Type:	Journal Article
Publication:	BRITISH JOURNAL OF PHARMACOLOGY
Publisher:	WILEY-BLACKWELL
Additional Information:	copyright for this article belongs to WILEY-BLACKWELL USA
Keywords:	methionine; osteoclast; RANKL; MyD88; alendronate; osteoporosis
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	20 Jan 2014 08:24
Last Modified:	20 Jan 2014 08:24
URI:	http://eprints.iisc.ac.in/id/eprint/48196

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