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, (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 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-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 IMPLICATIONSTLR-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.
AbbreviationsCTX, C-terminal telopeptides; MIP-1α, macrophage inhibitory protein-1α; MyD88, myeloid differentiation primary response gene 88; NFATc1, nuclear factor of activated T-cells; OVX, ovariectomized; TNFSF11, receptor activator of NF-κB ligand (also known as RANKL); TLR, toll-like receptor; TRAP5b, tartrate-resistant acid phosphatase 5b
Alzheimer's disease (AD) is the largest unmet medical complication. The devastation caused by the disease can be assumed from the disease symptoms like speech impairment, loss of self-awareness, acute memory loss etc. The individuals suffering from AD completely depend on caregivers and have to bear the high cost of treatment which increases the socio-economic burden on the society. Recent studies have shown that radiation exposure can have therapeutic effects when given in suitable amount for a specific time period. Therefore, we investigated the role of gamma irradiation in AD pathogenesis. The effect of radiation on amelioration of disease progression was studied in AD transgenic mice model (APP/PS1). Our
in-vivo
studies using APP/PS1 mice demonstrated that a single dose of 4.0 Gy gamma irradiation improves AD associated behavioral impairment. Radiation exposure also increased the level of anti-oxidant enzymes and reduced the astrocyte activation in the brain of APP/PS1 mice. A significant reduction was observed in AD associated proteins (APP, pTau, BACE) and neurofibrillary tangle formations (NFTs). Exposure to a single dose of 4 Gy gamma radiation also increased glucose metabolic functionality in AD transgenic mouse model. The kinases involved in insulin signaling such as GSK, ERK and JNK were also found to be modulated. However, an increased level of GSK3β (ser 9) was observed, which could be responsible for downregulating ERK and JNK phosphorylation. This resulted in a decrease in neurofibrillary tangle formations and amyloid deposition. The reduced hyperphosphorylation of Tau can be attributed to the increased level of GSK3β (ser 9) downregulating ERK and JNK phosphorylation. Thus, a single dose of 4 Gy gamma irradiation was found to have therapeutic benefits in treating AD
via
potentiating insulin signaling in APP/PS1 transgenic mice.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.