title: Expression of metalloproteinase-13 (Collagenase-3) is induced during fracture healing in mice.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Niigata University School of Medicine, Japan. ymgw@med.niigata-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Yamagiwa
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
authors.forename: T
authors.initials: T
authors.lastname: Hayami
authors.forename: H
authors.initials: H
authors.lastname: Hatano
authors.forename: M
authors.initials: M
authors.lastname: Uchida
authors.forename: N
authors.initials: N
authors.lastname: Endo
authors.forename: H E
authors.initials: HE
authors.lastname: Takahashi
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology*; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13; D051379:Mice; D008813:Mice, Inbred ICR; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012253:Rib Fractures / Q000201:enzymology* / Q000473:pathology; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D015675:Osteocalcin; D053495:Osteopontin; D003094:Collagen; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse