title: MCP1 triggers monocyte dysfunctions during abnormal osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis.
abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by pathological osteogenesis and inflammation. However, the pathogenesis of AS and the pathological relationship between osteogenesis and inflammation in this disease remain largely unknown. Mesenchymal stem cells (MSCs) are multipotent progenitor cells capable of osteogenic differentiation and immunoregulation. Recently, we demonstrated that MSCs from AS patients (ASMSCs) have a greater potential for osteogenic differentiation than MSCs from healthy donors (HDMSCs), which therefore seems to be a component of pathological osteogenesis in AS. Previous studies have indicated that the immunoregulatory abilities of MSCs change following differentiation. However, the subsequent effects of ASMSCs during abnormal osteogenic differentiation are unclear. Here, we further demonstrated that ASMSCs secreted more monocyte chemoattractant protein 1 (MCP1) than HDMSCs during osteogenic differentiation. This enhanced MCP1 secretion augmented monocyte migration, increased classical macrophage polarization, and enhanced TNF-α secretion. Inhibiting MCP1 secretion from osteogenic differentiated ASMSCs using lentiviruses encoding short hairpin RNAs ameliorated these dysfunctions. Blocking the ERK1/2 pathway in ASMSCs with U0126 corrected the abnormal osteogenic differentiation, inhibited MCP1 overexpression, and prevented subsequent monocyte dysfunction. Finally, MCP1 expression was up-regulated during osteogenic differentiation in ASMSCs in vivo and was locally augmented in osteoblasts at ossification sites in AS patients. In summary, our study determined that MCP1 overexpression during abnormal osteogenic differentiation of ASMSCs triggers monocyte dysfunctions. We propose the novel hypothesis that pathological osteogenesis can lead to inflammation in AS. This hypothesis may contribute to reveal the precise pathological relationship between osteogenesis and inflammation in the field of osteoimmunology.
  
  
  
  ASMSCs secreted more MCP1 during abnormal osteogenic differentiation. MCP1 overexpression leads to monocyte dysfunctions. Pathological osteogenesis can lead to inflammation in AS.
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Jinteng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Suhe
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Shuizhong
authors.initials: S
authors.lastname: Cen
authors.affiliation: Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Su
authors.affiliation: Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China. wuyanfengcn@126.com.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107# Yan Jiang Road West, Guangzhou, 510120, People's Republic of China. shenhuiy@yeah.net.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis; D034741:RNA, Small Interfering / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002070:Butadienes; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D009570:Nitriles; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126
keywords: Ankylosing spondylitis; Mesenchymal stem cells; Monocyte; Monocyte chemoattractant protein 1