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Methotrexate reversed synovial expression in early RA patients
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Methotrexate therapy reversed a high receptor activator of the Nf-kB ligand and osteoprotegerin ratio, a characteristic in the synovial membrane of early untreated rheumatoid arthritis patients, according to recent study results.
Researchers in Sweden studied 15 patients (median age, 56 years; 10 women) with newly diagnosed rheumatoid arthritis (RA; median symptom duration, 7 months) who received 20 mg methotrexate (MTX) weekly. Needle arthroscopy was used to gather synovial biopsies at baseline and 8 weeks after starting therapy. At baseline and 1 year after initiation, X-rays of patients’ hands and feet were conducted.
Detection of the receptor activator of the NF-kB ligand (RANKL), receptor activator of the nuclear factor KB (RANK) and osteoprotegerin (OPG) in the synovial biopsies were determined through immunohistochemistry. MTX therapy’s effect was tested on RA-derived primary fibroblasts, in osteoclasts and on the osteoblasts-like osteosarcoma cell line. It resulted in reduced synovial cellularity, RANK expression and RANK/OPG ratio. The mRNA and protein RANK/OPG ratio in synovial-deprived fibroblasts and osteoblasts-like tumoral cells exposed in vitro to methotrexate also decreased, which confirmed the effect.
“Supernatants from MTX-treated osteoblasts-like tumoral cells prevented pre-osteoclast formation in the absence of exogenous RANKL,” the researchers reported.
Despite microphage colony stimulating factor and RANKL presence, MTX blocked osteoclastogenesis from peripheral blood mononuclear cells, indicating its direct inhibition of osteoclastogenesis.
“We demonstrated that untreated, early RA is characterized by an imbalanced synovial expression of RANKL, RANK and OPG independent of local inflammation,” the researchers concluded. “This could be reverted by MTX treatment in some but not all patients. Methotrexate prevents osteoclastogenesis by a dual mechanism involving both reduction of RANKL expression and direct effects on osteoclasts precursors independent of RANKL.”
Disclosure: The researchers report no relevant financial disclosures.
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