Hsiu-Jung Liao1, I-Tsu Chyuan1, Chien-Sheng Wu1, Shu-Wha Lin1, Kun-Hung Chen1, Hwei-Fang Tsai2, Ping-Ning Hsu3. 1. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 2. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan hftsai8635@yahoo.com.tw. 3. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Immunology, College of Medicine, National Taiwan University, Division of Rheumatology, Department of Internal Medicine, Cathay General Hospital, Division of Rheumatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Department of Internal Medicine, Taipei Medical University, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Abstract
OBJECTIVE: Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is involved in macrophage activation, neutrophil motility and osteoclast differentiation. However, the role of PSTPIP2 in inflammation and autoinflammatory diseases is still not clear. In this study, we generated PSTPIP2 knockout (Pstpip2(-/-)) mice to investigate its phenotype and role in autoinflammatory diseases. METHODS: We constructed a Pstpip2-targeting vector and generated Pstpip2(-/-) mice. The phenotype and immunopathology of Pstpip2(-/-) mice were analysed. RESULTS: All Pstpip2(-/-) mice developed paw swelling, synovitis, hyperostosis and osteitis, resembling SAPHO syndrome, an inflammatory disorder of the bone, skin and joints. Multifocal osteomyelitis was found in inflamed paws, with increased macrophage and marked neutrophil infiltrations in the bone, joint and skin. Profound osteolytic lesions with markedly decreased bone volume density developed in paws and limbs. Neutrophil-attracting chemokines and IL-1β were markedly elevated in inflamed tissues. CONCLUSION: Our study suggests that PSTPIP2 could play a role in innate immunity and development of autoinflammatory bone disorders, and may be associated with the pathogenesis of human SAPHO syndrome.
OBJECTIVE:Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is involved in macrophage activation, neutrophil motility and osteoclast differentiation. However, the role of PSTPIP2 in inflammation and autoinflammatory diseases is still not clear. In this study, we generated PSTPIP2 knockout (Pstpip2(-/-)) mice to investigate its phenotype and role in autoinflammatory diseases. METHODS: We constructed a Pstpip2-targeting vector and generated Pstpip2(-/-) mice. The phenotype and immunopathology of Pstpip2(-/-) mice were analysed. RESULTS: All Pstpip2(-/-) mice developed paw swelling, synovitis, hyperostosis and osteitis, resembling SAPHO syndrome, an inflammatory disorder of the bone, skin and joints. Multifocal osteomyelitis was found in inflamed paws, with increased macrophage and marked neutrophil infiltrations in the bone, joint and skin. Profound osteolytic lesions with markedly decreased bone volume density developed in paws and limbs. Neutrophil-attracting chemokines and IL-1β were markedly elevated in inflamed tissues. CONCLUSION: Our study suggests that PSTPIP2 could play a role in innate immunity and development of autoinflammatory bone disorders, and may be associated with the pathogenesis of human SAPHO syndrome.
Authors: Pieter A Valkema; Clare H Luymes; Janneke E Witteveen; Saskia le Cessie; Natasha M Appelman-Dijkstra; Pancras C W Hogendoorn; Neveen A T Hamdy Journal: Orphanet J Rare Dis Date: 2017-01-25 Impact factor: 4.123