Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury

• Published in: PloS one Vol. 7; no. 7; p. e40602
• Main Authors: Loiselle, Alayna E, Frisch, Benjamin J, Wolenski, Matthew, Jacobson, Justin A, Calvi, Laura M, Schwarz, Edward M, Awad, Hani A, O'Keefe, Regis J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.07.2012; Public Library of Science (PLoS)
• Subjects: Adhesion; Animals; Biology; Biomechanics; Bone marrow; Bone Marrow Cells - enzymology; Bone marrow transplantation; Bone matrix; Cell migration; Cell Movement - physiology; Clonal deletion; Collagen; Collagen (type I); Collagen (type III); Dentistry; Female; Fibroblasts; Fibrosis; Gelatinase B; Gene expression; Gene Expression Regulation; Genes; Genetic engineering; Growth differentiation factor 5; Healing; Inflammation; Injuries; Injury prevention; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Medicine; Metalloproteinase; Mice; Mice, Knockout; Nervous system; Nonsteroidal anti-inflammatory drugs; Pathogenesis; Repair; Scars; Skin & tissue grafts; Stem cell transplantation; Stem cells; Tendon Injuries - enzymology; Tendon Injuries - pathology; Tendons; Tensile Strength; Tissue Adhesions; Wound Healing - genetics; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040602

The pathogenesis of adhesions following primary tendon repair is poorly understood, but is thought to involve dysregulation of matrix metalloproteinases (Mmps). We have previously demonstrated that Mmp9 gene expression is increased during the inflammatory phase following murine flexor digitorum (FDL) tendon repair in association with increased adhesions. To further investigate the role of Mmp9, the cellular, molecular, and biomechanical features of healing were examined in WT and Mmp9(-/-) mice using the FDL tendon repair model. Adhesions persisted in WT, but were reduced in Mmp9(-/-) mice by 21 days without any decrease in strength. Deletion of Mmp9 resulted in accelerated expression of neo-tendon associated genes, Gdf5 and Smad8, and delayed expression of collagen I and collagen III. Furthermore, WT bone marrow cells (GFP(+)) migrated specifically to the tendon repair site. Transplanting myeloablated Mmp9(-/-) mice with WT marrow cells resulted in greater adhesions than observed in Mmp9(-/-) mice and similar to those seen in WT mice. These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured tendons. Mmp9 is a potential target to limit adhesion formation in tendon healing.