Type III collagen modulates fracture callus bone formation and early remodeling

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.

Exploring platelet lysate hydrogel-coated suture threads as biofunctional composite living fibers for cell delivery in tissue repair

“…Collagen type I is a key protein in the ECM of several tissues of the human body, including bone, skin, tendons and ligaments. Furthermore, collagen type III is involved in the regulation of collagen type I fibrillogenesis and in tissue repair through a temporospatial coordinated expression during healing phases [35,36]. In this work, hASCs strongly expressed and deposited both collagen types, further suggesting a highly supportive role of PL to maintain cellular functions over time in culture.…”

Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases

“…The authors concluded that these findings implied that type III collagen is involved in the formation of the trabecular bone. Furthermore, using a bilateral tibial fracture model in the heterozygous (Col3a1 +/− ) mice reduced levels of Col3a1 were shown to impair the bone formation and alter remodelling during the healing of the fractures (Miedel et al, 2015). Based on immunofluorescent staining, fracture callus contained considerable amounts of type III collagen, whereas very little or no type III collagen was detected in the uninjured cortical bone.…”

Effects of alendronate in bone repair: A study in rat femur fractures treated with plates and screws

“…Reduced collagen III has been demonstrated to decrease bone formation and remodeling alterations during fracture healing. In 2015, Miedel et al (35) showed that collagen III levels begin to increase in the rst two days following a long bone fracture and remain elevated for the rst three weeks; the collagen can be found throughout immature woven bone of murine fracture callus, although it is less prevalent (by comparison) in the cartilaginous matrix. ALN act increasing bone volume and the level of mature collagen I reserve (36).…”