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Type III collagen modulates fracture callus bone formation and early remodeling
Authors:Todd Hamilton  Hadley Gleason  Gary P. Swain  Luke Lopas  Derek Dopkin  Joseph E. Perosky  Kenneth M. Kozloff  Kurt D. Hankenson  Susan W. Volk
Affiliation:1. Department of Clinical Studies‐Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;2. Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;3. Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, Michigan;4. Department of Physiology, Michigan State University, East Lansing, Michigan;5. Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan;6. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
Abstract:
Type III collagen (Col3) has been proposed to play a key role in tissue repair based upon its temporospatial expression during the healing process of many tissues, including bone. Given our previous finding that Col3 regulates the quality of cutaneous repair, as well as our recent data supporting its role in regulating osteoblast differentiation and trabecular bone quantity, we hypothesized that mice with diminished Col3 expression would exhibit altered long‐bone fracture healing. To determine the role of Col3 in bone repair, young adult wild‐type (Col3+/+) and haploinsufficent (Col3+/?) mice underwent bilateral tibial fractures. Healing was assessed 7, 14, 21, and 28 days following fracture utilizing microcomputed tomography (microCT), immunohistochemistry, and histomorphometry. MicroCT analysis revealed a small but significant increase in bone volume fraction in Col3+/? mice at day 21. However, histological analysis revealed that Col3+/? mice have less bone within the callus at days 21 and 28, which is consistent with the established role for Col3 in osteogenesis. Finally, a reduction in fracture callus osteoclastic activity in Col3+/? mice suggests Col3 also modulates callus remodeling. Although Col3 haploinsufficiency affected biological aspects of bone repair, it did not affect the regain of mechanical function in the young mice that were evaluated in this study. These findings provide evidence for a modulatory role for Col3 in fracture repair and support further investigations into its role in impaired bone healing. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:675–684, 2015.
Keywords:type III collagen  fracture  extracellular matrix
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