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  • 1
    ISSN: 1432-0827
    Keywords: Key words: Cathepsin — Chondrocyte — Fracture callus — Matrix metalloproteinase — Osteoclast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Fracture repair provides an interesting model for chondrogenesis and osteogenesis as it recapitulates in an adult organism the same steps encountered during embryonic skeletal development and growth. The fracture callus is not only a site of rapid production of cartilage and bone, but also a site of extensive degradation of their extracellular matrices. The present study was initiated to increase our understanding of the roles of different proteolytic enzymes, cysteine cathepsins B, H, K, L, and S, and matrix metalloproteinases (MMPs) 9 and 13, during fracture repair, as this aspect of bone repair has previously received little attention. Northern analysis revealed marked upregulation of cathepsin K, MMP-9, and MMP-13 mRNAs during the first and second weeks of healing. The expression profiles of these mRNAs were similar with that of osteoclastic marker enzyme tartrate-resistant alkaline phosphatate (TRAP). The changes in the mRNA levels of cathepsins B, H, L, and S were smaller when compared with those of the other enzymes studied. Immunohistochemistry and in situ hybridization confirmed the predominant localization of cathepsin K and MMP-9 and their mRNA in osteoclasts and chondroclasts at the osteochondral junction. MMP-13 was present in osteoblasts and individual hypertrophic chondrocytes near the cartilage-bone interphase. In cartilaginous callus, the expression of cathepsins B, H, L, and S was mainly related to chondrocyte hypertrophy. During bone remodeling both osteoblasts and osteoclasts contained these cathepsins. The present data demonstrate that degradation and remodeling of extracellular matrices during fracture healing involves activation of MMP-13 production in hypertrophic chondrocytes and osteoblasts, and cathepsin K and MMP-9 production in osteoclasts and chondroclasts.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0021-9304
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: The applicability of bioactive glass (BG) granules as a substitute for bone grafts was tested by comparing the histologic, histomorphometric, and molecular biologic healing patterns to those of bone autografts and ungrafted bone defects in a rat model. The cellular response in defects filled with BG granules was characterized by continuous overexpression of type III collagen. Osteogenic mesenchymal cells, prior to their differentiation to osteoblasts, organized as a dense periosteumlike layer on the surface of the BG granules. By day 14 new bone formation was more extensive in autografted defects than in BG filled defects (p = 0.039). No cartilage-specific type II collagen mRNA was detectable, confirming the uniformity of intramembranous bone formation. The difference in the initiation of new bone formation was further confirmed by the mRNA analyses of the de novo production of TGF-β1 and type I collagen. Autografted defects demonstrated the highest levels of TGF-β1 and type I collagen mRNAs during the first 2 weeks of healing, whereas BG-filled defects showed biphasic expression patterns of the same genes. Spontaneous new bone formation in ungrafted bone defects was also characterized by biphasic expression of type I collagen gene. Osteonectin mRNA declined gradually over time in autografted and BG filled defects, whereas unfilled defects showed a gradual increase of osteonectin mRNA during healing. By 8 weeks, about 70% of the BG surface showed evidence of direct new bone contact. Energy-dispersing X-ray analyses confirmed the presence of silica-rich and CaP-rich zones at the bonding interface. In conclusion, the osteoconductive surface of bioactive glass granules efficiently bonds to ongrowing new bone but the material does not reach the capacity of autogenous bone graft in promotion of osteogenesis. © 1997 John Wiley & Sons, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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