ABSTRACT
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.
Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Methionine/pharmacology , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Osteoclasts/drug effects , Osteoporosis/prevention & control , Signal Transduction/drug effects , Toll-Like Receptor 4/drug effects , Acid Phosphatase/metabolism , Administration, Oral , Alendronate/pharmacology , Animals , Bone Density/drug effects , Bone Density Conservation Agents/administration & dosage , Cells, Cultured , Chemokine CCL3/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Down-Regulation , Drug Therapy, Combination , Female , Inflammation Mediators/metabolism , Isoenzymes/metabolism , Methionine/administration & dosage , Myeloid Differentiation Factor 88/genetics , Osteoclasts/metabolism , Osteoporosis/genetics , Osteoporosis/metabolism , Osteoporosis/physiopathology , Ovariectomy , RNA Interference , Rats , Rats, Sprague-Dawley , Tartrate-Resistant Acid Phosphatase , Time Factors , Toll-Like Receptor 4/metabolismABSTRACT
An unusual case of recurrent condyloma acuminatum in a tubular penile piercing scar is presented. This case documents a previously unreported dermatologic infectious sequela of this practice. We comment on complications of bodily and genital piercing.
Subject(s)
Condylomata Acuminata/etiology , Penis/injuries , Adult , Esthetics , Humans , Male , RecurrenceABSTRACT
Spindle cell carcinoma of the penis has been documented by light microscopy only once in the past. This case report illustrates the light and electron microscopy of a second case. Contrary to previously expressed opinions, polypoid spindle cell carcinomas are not necessarily associated with a good prognosis.
