Human gingival tissue-derived MSC suppress osteoclastogenesis and bone erosion via CD39-adenosine signal pathway in autoimmune arthritisResearch in context
Yang Luo,
Wenbin Wu,
Jian Gu,
Ximei Zhang,
Junlong Dang,
Julie Wang,
Yongjiang Zheng,
Feng Huang,
Jia Yuan,
Youqiu Xue,
Qingling Fu,
Umadevi Kandalam,
Jacob Colello,
Song Guo Zheng
Affiliations
Yang Luo
Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou 510000, PR China; Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA; Department of Neurology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, PR China
Wenbin Wu
Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou 510000, PR China
Jian Gu
Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA; Division of Rheumatology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Ximei Zhang
Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou 510000, PR China; Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA; Division of Rheumatology and Immunology, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, PA 43201, USA
Junlong Dang
Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou 510000, PR China; Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA
Julie Wang
Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA; Division of Rheumatology and Immunology, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, PA 43201, USA
Yongjiang Zheng
Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA
Feng Huang
Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou 510000, PR China
Jia Yuan
Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou 510000, PR China
Youqiu Xue
Department of Clinical Immunology, Sun Yat-sen University Third Affiliated Hospital, Guangzhou 510000, PR China; Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA; Division of Rheumatology and Immunology, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, PA 43201, USA
Qingling Fu
Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, PR China
Umadevi Kandalam
Department of Pediatric Dentistry, College of Dental Medicine, Nova Southeastern University, Davie, FL 33328, USA
Jacob Colello
Division of Rheumatology, Department of Medicine at Penn State College of Medicine and Milton S. Hershey Medical Center, Hershey 17033, USA
Song Guo Zheng
Division of Rheumatology and Immunology, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, PA 43201, USA; Corresponding author at: Ohio State University College of Medicine and Wexner Medical Center, 480 Medical Center Dr, Columbus, OH 43201, USA.
Background: Bone destruction is one of many severe complications that occurs in patients with rheumatoid arthritis (RA) and current therapies are unable to cure this manifestation. This study here aims to determine whether GMSC can directly inhibit osteoclast formation and eventually attenuate osteoclastogenesis and bone erosion in an inflammatory milieu. Method: GMSC were co-cultured with osteoclast precursors with or without CD39 inhibitor, CD73 inhibitor or adenosine receptors inhibitors pretreatment and osteoclast formation were evaluated in vitro. 2×10^6 GMSC per mouse were transferred to CIA mice and pathology scores, the frequency of osteoclasts, bone erosion in joints were assessed in vivo. Finding: GMSC but not control cells, markedly suppressed human or mice osteoclastogenesis in vitro. GMSC treatment also resulted in a dramatically decreased level of NF-κB p65/p50 in osteoclasts in vitro. Infusion of GMSC to CIA significantly attenuated the severity of arthritis, pathology scores, frequency of osteoclasts, particularly bone erosion, as well as a decreased expression of RANKL in synovial tissues in vivo. Blockade of CD39/CD73 or adenosine receptors has significantly abrogated the suppressive ability of GMSC in vitro and therapeutic effect of GMSC on bone erosion during CIA in vivo. Interpretation: GMSC inhibit osteoclast formation in vitro and in vivo partially via CD39-CD73-adenosine signals. Manipulation of GMSC may have a therapeutic implication on rheumatoid arthritis and other bone erosion related diseases. Fund: This study was supported by grants from the National Key R&D Program of China (2017YFA0105801 to F.H); the Zhujiang Innovative and Entrepreneurial Talent Team Award of Guangdong Province (2016 ZT 06S 252 to F·H) and National Institutes of Health (R01 AR059103, R61 AR073409 and NIH Star Award to S.G.Z). Keywords: Rheumatoid arthritis, Mesenchymal stem cells, CD39, Adenosine
