title: Altered function in cartilage derived mesenchymal stem cell leads to OA-related cartilage erosion.
abstract: A portion of osteoarthritis (OA) patients with total knee arthroplasty (TKA) had monocondylar destruction in medial femoral condyle, but healthy-appearant cartilage in lateral side. However, there is limited information concerning functional differences of cartilage derived mesenchymal stem cell (CMSC) between these two locations in the same donor and its possible role in the pathogenesis of OA. Cells isolated from the degraded cartilage in medial condyle and normal cartilage in lateral side from OA patients were identified with co-expressed markers CD105 and CD166 and confirmed as CMSCs by immunophenotype. The relative percentage, proliferation activity, multi-lineage differentiation potential and miRNA expression profile of CMSCs in two groups were compared by flow cytometry, CCK-8 assay, cytochemical staining, immunohistochemistry, real-time PCR and miRNA microarray analysis. Our study suggested that the percentage (10.61±6.97% vs. 18.44±9.97%, P<0.05) and proliferation rate (P<0.01) of CD105+/CD166+ CMSCs from the degraded cartilage were significantly reduced compared with those from the normal cartilage. CMSCs from the degraded cartilage also showed stronger osteogenic (P<0.05), weaker adipogenic (P<0.01), and comparable chondrogenic potential (P>0.05) during differentiation. MiR-31-5p and miR-424-5p were down regulated in CMSCs from the degraded cartilage. In conclusion, altered function such as reduced percentage and proliferation ability, as well as changes in differentiation profile of CMSC contributed to homeostasis imbalance, leading to OA-related cartilage erosion. Furthermore, regulatory networks of multiple miRNAs may be partially responsible for the dysfunction of CMSCs.
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Zenan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical SciencesNo.1 Shuaifuyuan, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Bone and Joint DiseaseNo.1 Shuaifuyuan, Beijing 100730, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing 100050, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical SciencesNo.1 Shuaifuyuan, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Bone and Joint DiseaseNo.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical SciencesNo.1 Shuaifuyuan, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Bone and Joint DiseaseNo.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Bupeng
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Yufen
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences No.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical SciencesNo.1 Shuaifuyuan, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Bone and Joint DiseaseNo.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Guixing
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Department of Orthopaedic Surgery, West China Hospital, Sichuan University Chengdu 610041, Sichuan Province, China.
authors.forename: Shishu
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical SciencesNo.1 Shuaifuyuan, Beijing 100730, China; Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical SciencesNo.1 Shuaifuyuan, Beijing 100730, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
keywords: Osteoarthritis; cartilage derived mesenchymal stem cell; miR-31-5p; miR-424-5p; multi-lineage differentiation potential