MicroRNAs are non-coding small RNAs that reportedly regulate mRNA targets or protein translation of various tissues in physiological and pathological contexts. This study was undertaken to characterise the contributions of microRNA-29a (miR-29a) to the progression of estrogen deficiency-mediated excessive osteoclast resorption and bone loss. Osteoblast-specific transgenic mice overexpressing miR-29a driven by osteocalcin promoter (C57BL/6JNarl-TgOCN-mir29a) or wild-type mice were subjected to bilateral ovariectomy. Bone mineral density, trabecular microarchitecture and osteoclast distribution was quantified by μCT and histomorphometry. Primary CD11b+CSF-1R+ preosteoclasts were isolated for detecting ex vivo osteoclast differentiation. Gene expression and transcription factor-promoter interaction were quantified by RT-PCR and chromatin immunoprecipitation.Background
Methods
Methotrexate chemotherapy (commonly used in treating cancers and rheumatoid arthritis) creates an inflammatory condition in bone, decreasing osteogenesis, enhancing adipogenesis, increasing osteoclastogenesis, leading to bone loss and marrow adiposity; treatment with fish oil or folinic acid counteracts these negative effects and prevents bone loss. Chemotherapy with anti-metabolite methotrexate (MTX) is commonly used in treating cancers and rheumatoid arthritis; however it is known to cause bone loss for which currently there are no adjunct preventative treatments.Summary
Introduction
