Advances in the role and mechanism of fibroblasts in fracture healing

Abstract

With the development of social population ageing, bone fracture has become a global public health problem due to its high morbidity, disability and mortality. Fracture healing is a complex phenomenon involving the coordinated participation of immigration, differentiation and proliferation of inflammatory cells, angioblasts, fibroblasts, chondroblasts and osteoblasts which synthesize and release bioactive substances of extracellular matrix components, Mortality caused by age-related bone fractures or osteoporosis is steadily increasing worldwide as the population ages. Fibroblasts play an important role in the process of fracture healing. However, it is not clear how the growth factors and extracellular matrix stiffness of the bone-regeneration microenvironment affects the function of osteoblasts and fibroblasts in healing process. Therefore, this article focuses on the role of fibroblasts in the process of fracture healing and mechanisms of research progress.

Keywords: bone microenvironment; cytokines; fibroblasts; fracture healing; osteoblasts.

Figure 1

Schematic description of the four phases of fracture healing with sequential need for growth factor. Bone healing can be viewed as a three-stage biological phase (inflammation, repair, and remodelling) which can be further divided into six main sub-steps: hematoma, inflammation, soft callus formation, hard callus formation, remodelling, bone healing. Immune cells are activated and recruited towards the fracture gap. Platelet derived growth factor (PDGF) acts in recruitment and proliferation of mesenchymal stem cells/osteoprogenitor cells. Activation of cytokine, for instance, (VEGF) also paves the way for angiogenesis. Bone morphogenic protein-2 (BMP-2) promotes osteoblastic and chondrocyte differentiation. Fibroblast growth factor-2 (FGF-2) acts mitogenic on MSC/OPC, osteoblasts, chondrocytes and osteoclasts, and enhances matrix synthesis and angiogenesis. Fibroblast growth factor 23 (FGF-23) inhibits osteoblast differentiation and matrix synthesis. IGF, PDGF, and VEGF promote the increase activity of osteoblast proliferation and differentiation. TGFβ has a positive effect to bone remodelling through regulation of both osteoblasts and osteoclasts.