Expression of metalloproteinase-13 (Collagenase-3) is induced during fracture healing in mice

Bone. 1999 Aug;25(2):197-203. doi: 10.1016/s8756-3282(99)00157-x.


In fracture healing, a large amount of cartilage is formed, then rapidly replaced by osseous tissue. This process requires the transition of extracellular matrix component from type II to type I collagen. We investigated the expression of matrix metalloproteinase-13 (MMP-13), which has a high potential to cleave type II as well as type I collagen, during fracture repair in mouse ribs. In situ hybridization demonstrated that MMP-13 mRNA was present throughout the healing process. It was detected in the cells of the periosteum at day 1. As fracture callus grew, strong MMP-13 mRNA signals were detected in cells of the cartilaginous callus. In the reparative and remodeling phases, both hypertrophic chondrocytes and immature osteoblastic cells in the fracture callus expressed MMP-13 mRNA strongly. These cells were located adjacent to tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts at the sites of cartilage/bone transition. In osteoclasts, MMP-13 expression was not detected. The level of MMP-13 mRNA peaked at day 14 postfracture by northern blotting. Immunohistochemical staining showed that MMP-13 was detected primarily in hypertrophic chondrocytes. These results indicate that MMP-13 is induced during fracture healing. The site- and cell-specific expression of MMP-13 and its enzymatic property suggest that MMP-13 initiates the degradation of cartilage matrix, resulting in resorption and remodeling of the callus. In conclusion, MMP-13 plays an important role in the healing process of fractured bone in mice.

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Blotting, Northern
  • Chondrocytes / cytology
  • Chondrocytes / enzymology
  • Collagen / genetics
  • Collagen / metabolism
  • Collagenases / biosynthesis*
  • Collagenases / genetics
  • DNA Primers / chemistry
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Fracture Healing / physiology*
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Isoenzymes / metabolism
  • Male
  • Matrix Metalloproteinase 13
  • Mice
  • Mice, Inbred ICR
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteopontin
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rib Fractures / enzymology*
  • Rib Fractures / pathology
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / metabolism
  • Tartrate-Resistant Acid Phosphatase


  • DNA Primers
  • Extracellular Matrix Proteins
  • Isoenzymes
  • RNA, Messenger
  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Osteocalcin
  • Osteopontin
  • Collagen
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Collagenases
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse