Increase in TPSB2 and TPSD1 Expression in Synovium of Hip Osteoarthritis Patients Who Are Overweight

While research suggests that increasing body mass index (BMI) is a risk factor for hip osteoarthritis (HOA), the mechanisms of this effect are not fully understood. Tryptases are among the main proteases found in mast cells (MCs) and contribute to OA pathology. TPSB2, which encodes β-tryptase, is increased in the synovium of overweight and obese knee OA patients. However, it remains unclear whether tryptase in the synovium of HOA is increased with increasing BMI. Here, we investigated tryptase genes (TPSB2 and TPSD1) in the synovium of overweight HOA patients. Forty-six patients radiographically diagnosed with HOA were allocated to two groups based on BMI, namely normal (<25 kg/m2) and overweight (25–29.99 kg/m2). TPSB2 and TPSD1 expression in the synovium of the two groups was compared using real-time polymerase chain reaction. To compare TPSB2 and TPSD1 expression in MCs between the groups, we isolated the MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF), extracted using magnetic isolation. TPSB2 and TPSD1 expression was increased in the overweight group compared with the normal group. Expression of both genes in the MC-RF was significantly higher than that in MC-PF in both groups. However, TPSB2 and TPSD1 expression levels in the MC-RF did not differ between the groups. Tryptase genes were highly expressed in the synovium of overweight HOA patients. Further investigation to reveal the role of tryptase in the relationship between increasing BMI and HOA pathology is required.

[1]  G. Jay,et al.  Tryptase β regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis , 2023, Nature Communications.

[2]  Simon W. Jones,et al.  Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets , 2023, Clinical and translational medicine.

[3]  Jinghua Wang,et al.  Prevalence and factors associated with knee osteoarthritis among middle-aged and elderly individuals in rural Tianjin: a population-based cross-sectional study , 2023, Journal of Orthopaedic Surgery and Research.

[4]  M. Nevitt,et al.  The Association of Metabolic Syndrome and Obesity With Clinical Hip Osteoarthritis in the Study of Osteoporotic Fractures and the Osteoporotic Fractures in Men Study Cohorts , 2023, ACR open rheumatology.

[5]  M. Mukai,et al.  Increased NMUR1 Expression in Mast Cells in the Synovial Membrane of Obese Osteoarthritis Patients , 2022, International journal of molecular sciences.

[6]  Jae-Min Park.  Association between obesity and osteoarthritis in the South Korean older population: A nationwide population-based study , 2022, Medicine.

[7]  C. Bock,et al.  Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease , 2022, Frontiers in Immunology.

[8]  E. Tycksen,et al.  RNA‐Seq analysis reveals sex‐dependent transcriptomic profiles of human subacromial bursa stratified by tear etiology , 2022, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  S. Young,et al.  Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses , 2022, International journal of molecular sciences.

[10]  N. Lane,et al.  Synovial inflammation in osteoarthritis progression , 2022, Nature Reviews Rheumatology.

[11]  M. Mukai,et al.  Increase in Tryptase and Its Role in the Synovial Membrane of Overweight and Obese Patients with Osteoarthritis of the Knee , 2020, Diabetes, metabolic syndrome and obesity : targets and therapy.

[12]  B. Yaspan,et al.  An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma , 2019, Cell.

[13]  W. Robinson,et al.  IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis , 2019, eLife.

[14]  K. Uchida,et al.  Increase in mast cell marker expression in the synovium of obese patients with osteoarthritis of the knee , 2019, Diabetes, metabolic syndrome and obesity : targets and therapy.

[15]  Navin D. Fernando,et al.  Classifications in Brief: Tönnis Classification of Hip Osteoarthritis , 2018, Clinical orthopaedics and related research.

[16]  Philip G Conaghan,et al.  Synovitis in osteoarthritis: current understanding with therapeutic implications , 2017, Arthritis Research & Therapy.

[17]  D. Hunter,et al.  Hip Osteoarthritis: Etiopathogenesis and Implications for Management , 2016, Advances in Therapy.

[18]  A. Mobasheri,et al.  Inflammatory mediators in osteoarthritis: A critical review of the state-of-the-art, current prospects, and future challenges. , 2016, Bone.

[19]  A. Oberg,et al.  Transcriptomic Profiles of High and Low Antibody Responders to Smallpox Vaccine , 2013, Genes and Immunity.

[20]  G. Hu,et al.  Mast Cell Tryptase Induces Microglia Activation via Protease-activated Receptor 2 Signaling , 2012, Cellular Physiology and Biochemistry.

[21]  Gavin C. Jones,et al.  The role of proteases in pathologies of the synovial joint. , 2008, The international journal of biochemistry & cell biology.

[22]  G. Caughey.  Mast cell tryptases and chymases in inflammation and host defense , 2007, Immunological reviews.

[23]  T. Nikawa,et al.  Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis , 2007, Clinical Rheumatology.

[24]  G. Pejler,et al.  Biology of mast cell tryptase , 2006 .

[25]  L. Schwartz,et al.  Expression of α-tryptase and β-tryptase by human basophils , 2004 .

[26]  A. Ben-Yehudah,et al.  Tryptase activates peripheral blood mononuclear cells causing the synthesis and release of TNF-α, IL-6 and IL-1β: possible relevance to multiple sclerosis , 2003, Journal of Neuroimmunology.

[27]  A. Gelber.  Obesity and hip osteoarthritis: the weight of the evidence is increasing. , 2003, The American journal of medicine.

[28]  W. Bode,et al.  The structure of the human betaII-tryptase tetramer: fo(u)r better or worse. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M. Pallaoro,et al.  Characterization of Genes Encoding Known and Novel Human Mast Cell Tryptases on Chromosome 16p13.3* , 1999, The Journal of Biological Chemistry.

[30]  Simon W. Jones,et al.  Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis‐Associated Lung Adenocarcinoma Transcript 1 Long Noncoding RNA in Obese Patients With Osteoarthritis , 2020, Arthritis & rheumatology.

[31]  C. Sommerhoff,et al.  Mast cell tryptase beta as a target in allergic inflammation: an evolving story. , 2007, Current pharmaceutical design.