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

• Published in: Bone (New York, N.Y.) Vol. 25; no. 2; pp. 197 - 203
• Main Authors: Yamagiwa, H, Tokunaga, K, Hayami, T, Hatano, H, Uchida, M, Endo, N, Takahashi, H.E
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1999; Elsevier Science
• Subjects: Acid Phosphatase - metabolism; Animals; Biological and medical sciences; Blotting, Northern; Bone remodeling; Cartilage resorption; Chondrocytes - cytology; Chondrocytes - enzymology; Collagen - genetics; Collagen - metabolism; Collagenases - biosynthesis; Collagenases - genetics; DNA Primers - chemistry; Endochondral ossification; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Fracture healing; Fracture Healing - physiology; Fundamental and applied biological sciences. Psychology; Immunoenzyme Techniques; In Situ Hybridization; Isoenzymes - metabolism; Male; Matrix Metalloproteinase 13; Mice; Mice, Inbred ICR; MMP-13 (collagenase-3); Osteocalcin - genetics; Osteocalcin - metabolism; Osteopontin; Reverse Transcriptase Polymerase Chain Reaction; Rib Fractures - enzymology; Rib Fractures - pathology; RNA, Messenger - metabolism; Sialoglycoproteins - genetics; Sialoglycoproteins - metabolism; Skeleton and joints; Tartrate-Resistant Acid Phosphatase; Vertebrates: osteoarticular system, musculoskeletal system; Fracture healing; Bone remodeling; In situ hybridization; Endochondral ossification; MMP-13 (collagenase-3); Cartilage resorption; Immunohistochemistry; Animal model; In situ; Rodentia; Diseases of the osteoarticular system; Induced fracture; Exploration; Hybridization; Rib(bone); Pathology; Vertebrata; Histopathology; Mammalia; Consolidation; Mouse; Bone
• ISSN: 8756-3282; 1873-2763
• 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.