Ken Takata,1 Kentaro Uchida,1,2 Manabu Mukai,1 Shotaro Takano,1 Jun Aikawa,1 Dai Iwase,1 Hiroyuki Sekiguchi,2 Masayuki Miyagi,1 Gen Inoue,1 Masashi Takaso1 1Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan; 2Shonan University of Medical Sciences Research Institute, Chigasaki City, Kanagawa 253-0083, JapanCorrespondence: Kentaro Uchida Tel/Fax +81-42-778-9217Email kuchida@med.kitasato-u.ac.jpPurpose: The mechanisms governing evidence that obesity is a risk factor for osteoarthritis (OA) are not well understood. We previously reported an increase in mast cell (MC) marker expression in the osteoarthritic synovial membrane (SM) of patients with obesity. We hypothesized that an enzyme produced by MC, β-tryptase, may be increased in the SM of obese patients with knee OA and contribute to synovial inflammation. This study investigated the expression of the β-tryptase encoding gene, TPSB2, in the SM of obese patients with knee OA and β-tryptase-mediated regulation of IL-1β in synovial cells.Patients and Methods: A total of 216 patients radiographically diagnosed with knee OA were grouped according to the World Health Organization’s body mass index classifications: normal weight (NW; < 25 kg/m2), overweight (OW; 25– 29.99 kg/m2) and obese (OB; ≥ 30 kg/m2). Quantitative polymerase chain reaction was conducted to examine TPSB2 expression in the SM among the three groups. We also examined TPSB2 and IL1B expression in MC-rich (CD3-CD14-CD19-CD90-) and MC-poor (CD3+, CD14+, CD19+, or CD90+) fractions freshly isolated from synovial tissue. Further, the effect of β-tryptase on IL1B expression was investigated in cultured CD14-positive (macrophage-rich fraction) and CD14-negative (fibroblast-rich fraction) cells.Results: There was significantly elevated TPSB2 expression in the OW and OB groups compared to the NW group. The MC-rich fraction had significantly higher levels of TPSB2, CD117 and CD203c than the MC-poor fraction. Recombinant human β-tryptase stimulated IL1B expression in both the synovial fibroblast and macrophage fractions.Conclusion: Obese patients with knee OA showed elevated TPSB2 expression in the SM. Tryptase may play a role in synovial inflammation in obese patients with OA.Keywords: obese, mast cell, osteoarthritis, tryptase, synovial membrane
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