Yamagiwa H, Tokunaga K, Hayami T, Hatano H, Uchida M, Endo N, Takahashi H E
Department of Orthopedic Surgery, Niigata University School of Medicine, Japan.
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.
在骨折愈合过程中，会形成大量软骨，然后迅速被骨组织替代。这一过程需要细胞外基质成分从II型胶原蛋白转变为I型胶原蛋白。我们研究了基质金属蛋白酶-13（MMP-13）在小鼠肋骨骨折修复过程中的表达，该酶具有切割II型和I型胶原蛋白的高潜力。原位杂交表明，MMP-13 mRNA在整个愈合过程中均有表达。在第1天时，在骨膜细胞中检测到该基因。随着骨折骨痂的生长，在软骨痂细胞中检测到强烈的MMP-13 mRNA信号。在修复和重塑阶段，骨折骨痂中的肥大软骨细胞和未成熟成骨细胞均强烈表达MMP-13 mRNA。这些细胞位于软骨/骨转换部位的抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞附近。在破骨细胞中未检测到MMP-13表达。通过Northern印迹法检测到MMP-13 mRNA水平在骨折后第14天达到峰值。免疫组织化学染色显示，MMP-13主要在肥大软骨细胞中检测到。这些结果表明，MMP-13在骨折愈合过程中被诱导。MMP-13的位点和细胞特异性表达及其酶特性表明，MMP-13启动软骨基质的降解，导致骨痂的吸收和重塑。总之，MMP-13在小鼠骨折愈合过程中起重要作用。
