title: [Transplantation of adipose derived mesenchymal stem cells alleviated osteoarthritis induced with anterior cruciate ligament transection].
abstract: OBJECTIVE
  To explore the therapeutic potential of transplantation of adipose derived mesenchymal stem cells (ADMSCs) in rats osteoarthritis caused by anterior cruciate ligament transection.
  
  
  METHODS
  Rats peritoneal adipose tissues were used to extract ADMSCs.Cell morphological appearance was documented and flow cytometric cell cycle was used to identify ADMSCs. Anterior cruciate ligament transection was used to induce knee osteoarthritis in rats. ADMSCs were injected into the knee cavities. Knee joint pathology was performed to observe the treatment effects. QRT-PCR and Western blot were used to identify the targets of ADMSCs.
  
  
  RESULTS
  ADMSCs were successfully extracted, separated, cultured and identified. Two and eight weeks after ADMSCs transplantation, pathology showed significantly attenuation of arthritis including osteophyte and synovitis, reflecting in significantly improvement of both osteophyte and synovitis grading compared to the controls. QRT-PCR and Western blot revealed that collagen Ⅱ expression was significantly up-regulated after ADMSCs transplantation compared to the controls.MMP-13, but not other MMP-1, MMP-3 or MMP-9 was reduced when ADMSCs were co-cultured with primary chondrocytes. DDR-2 expression in chondrocyte was heavily up-regulated when stimulated by TNF-α in vitro. However, ADMSCs could reverse the effect when co-cultured with chondrocyte, implying that ADMSCs may suppress the expression of DDR-2. IL-1β suppressed the cartilage differentiation of ADMSCs, and Actinomycin D (DDR-2 inhibitor) could reverse the effect.
  
  
  CONCLUSIONS
  ADMSCs can attenuate osteoarthritis induced by anterior cruciate ligament transection in rats by suppressing the expression of MMP-13, and the upstream target spot may be DDR-2.
authors.affiliation: Department of Rheumatology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Cui
authors.forename: J W
authors.initials: JW
authors.lastname: Xie
authors.forename: J P
authors.initials: JP
authors.lastname: Li
authors.forename: J Y
authors.initials: JY
authors.lastname: Yang
authors.forename: H S
authors.initials: HS
authors.lastname: Xu
authors.forename: L Q
authors.initials: LQ
authors.lastname: Liang
authors.forename: X Y
authors.initials: XY
authors.lastname: Yang
authors.forename: F
authors.initials: F
authors.lastname: Lian
mesh_terms: D000273:Adipose Tissue; D050154:Adiposity; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D002358:Cartilage, Articular / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects*; D018920:Coculture Techniques; D053583:Interleukin-1beta; D007719:Knee Joint; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D009765:Obesity; D020370:Osteoarthritis, Knee; D051381:Rats; D014409:Tumor Necrosis Factor-alpha
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13