title: Ovine synovial membrane-derived mesenchymal progenitor cells retain the phenotype of the original tissue that was exposed to in-vivo inflammation: evidence for a suppressed chondrogenic differentiation potential of the cells.
abstract: BACKGROUND
  The purpose of this study was to characterize the effect of post-surgery joint inflammation on the chondrogenic differentiation capacity of mesenchymal progenitor cells (MPCs) derived from the synovial membrane (SM).
  
  
  METHODS
  Six Suffolk-cross sheep were subjected to experimental anterior cruciate ligament (ACL) core surgeries. After they were killed 2 weeks after surgery, the volume of synovial fluid in the knees was measured and SM was collected for mRNA extraction and cell isolation. Cells were propagated and used for lineage-specific differentiation assays using cell pellet cultures and mRNA extraction. Chondrogenic differentiation assays in the presence of exogenous interleukin-1β (IL-1β) were also performed.
  
  
  RESULTS
  The volume of synovial fluid from the operated knees was significantly greater than from the contralateral knees. Quantitative RT-PCR revealed that mRNA levels for IL-1β and matrix metalloproteinases-3 and -13 in SM from the operated knees were significantly higher than those from the contralateral knees. The size of MPC pellets from operated knees (opMPC) cultured in chondrogenic medium were significantly smaller than the corresponding pellets generated with MPCs from contralateral knees (conMPC). Addition of 1-100 ng/ml IL-1β significantly suppressed the resultant size of chondrogenic cell pellets from normal ovine SM-MPC.
  
  
  CONCLUSIONS
  From these results, we conclude that cells from SM exposed to post-surgical inflammation are compromised by the inflammatory environment and that IL-1β can inhibit the latent chondrogenic potential of normal MPCs. This suggests that if MPCs from injured joints do contribute to cartilage repair, their endogenous repair potential may become compromised by such post-injury joint inflammation.
authors.affiliation: Faculty of Medicine, McCaig Institute for Bone and Joint Health, University of Calgary, 3330 Hospital drive, NW, Calgary, AB, T2N4N1, Canada.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ando
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Heard
authors.forename: May
authors.initials: M
authors.lastname: Chung
authors.forename: Norimasa
authors.initials: N
authors.lastname: Nakamura
authors.forename: Cyril B
authors.initials: CB
authors.lastname: Frank
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D053583:Interleukin-1beta / Q000235:genetics / Q000494:pharmacology; D007596:Joints / Q000276:immunology / Q000601:surgery; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D010641:Phenotype; D012333:RNA, Messenger / Q000276:immunology; D012756:Sheep; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3