title: Toward understanding the role of cartilage particulates in synovial inflammation.
abstract: Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium.
  
  
  
  In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy.
  
  
  
  Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups.
  
  
  
  The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA. Electronic address: ams2396@columbia.edu.
authors.forename: A M
authors.initials: AM
authors.lastname: Silverstein
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA. Electronic address: rms2216@columbia.edu.
authors.forename: R M
authors.initials: RM
authors.lastname: Stefani
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA. Electronic address: es3351@columbia.edu.
authors.forename: E
authors.initials: E
authors.lastname: Sobczak
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA. Electronic address: elt2128@columbia.edu.
authors.forename: E L
authors.initials: EL
authors.lastname: Tong
authors.affiliation: Division of Rheumatology, Department of Medicine, New York University School of Medicine and NYU Langone Medical Center, New York, NY, USA. Electronic address: mukundan.attur@nyumc.org.
authors.forename: M G
authors.initials: MG
authors.lastname: Attur
authors.affiliation: Department of Orthopedic Surgery, Columbia University, New York, NY, USA. Electronic address: rs3464@cumc.columbia.edu.
authors.forename: R P
authors.initials: RP
authors.lastname: Shah
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY, USA. Electronic address: jcb4@biology.columbia.edu.
authors.forename: J C
authors.initials: JC
authors.lastname: Bulinski
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA; Department of Mechanical Engineering, Columbia University, New York, NY, USA. Electronic address: ateshian@columbia.edu.
authors.forename: G A
authors.initials: GA
authors.lastname: Ateshian
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA. Electronic address: cth6@columbia.edu.
authors.forename: C T
authors.initials: CT
authors.lastname: Hung
mesh_terms: D000818:Animals; D002356:Cartilage; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology; D007840:Latex; D008954:Models, Biological; D010587:Phagocytosis / Q000502:physiology; D013583:Synovial Membrane / Q000737:chemistry*; D013585:Synovitis / Q000473:pathology*
chemical_list: D016207:Cytokines; D007840:Latex
keywords: Cartilage; Inflammation; Synovium; Wear particles