Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury.
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.
Center for Musculoskeletal Research, University of Rochester, Rochester, New York, United States of America.
Alayna E
AE
Loiselle
Benjamin J
BJ
Frisch
Matthew
M
Wolenski
Justin A
JA
Jacobson
Laura M
LM
Calvi
Edward M
EM
Schwarz
Hani A
HA
Awad
Regis J
RJ
O'Keefe
D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology*; D002465:Cell Movement / Q000502:physiology; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013708:Tendon Injuries / Q000201:enzymology* / Q000473:pathology*; D013718:Tensile Strength; D000267:Tissue Adhesions; D014945:Wound Healing / Q000235:genetics
D020780:Matrix Metalloproteinase 9