title: Novel nonmatrix-metalloproteinase-mediated collagen degradation.
abstract: Matrix metalloproteinases (MMPs) and their inhibitors have long been believed to play a major role in the collagen loss seen in destructive temporomandibular joint (TMJ) disorders. This project was originally designed to examine the expression of MMPs and the tissue inhibitors of MMPs (TIMPs) by diseased human TMJ synovial fibroblasts and to determine their ability to degrade Type I collagen. Reverse transcriptase-PCR indicated that these TMJ synovial fibroblasts expressed mRNA for multiple MMPs and TIMPs. The collagen degradation assay showed that these TMJ synovial fibroblasts at passage 3 to 8 were capable of digesting the collagen underneath them on collagen-coated plates. This degradation was inhibited by GM6001, a synthetic MMP inhibitor. During passage 8 to 13, these TMJ fibroblasts were able to digest all the collagen in the wells. This degradation was completely inhibited by combining GM6001 and soybean trypsin inhibitor (STI), a serine proteinase inhibitor. The collagen cleavage activity of collected conditioned media was dramatically inhibited by STI but not by 1,10-phenanthroline, an MMP inhibitor. The data suggest that these TMJ cells utilize a MMP-dependent pathway and a novel MMP-independent pathway to digest Type I collagen.
authors.affiliation: Indiana University School of Dentistry, Department of Oral Biology, 1121 West Michigan Street, Room 271, Indianapolis, IN 46202, USA.
authors.forename: F
authors.initials: F
authors.lastname: Song
authors.forename: L J
authors.initials: LJ
authors.lastname: Windsor
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D013704:Temporomandibular Joint / Q000378:metabolism*; D013705:Temporomandibular Joint Disorders / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D003094:Collagen; D020782:Matrix Metalloproteinases