Chondrocyte BMP2 signaling plays an essential role in bone fracture healing

Abstract

The specific role of endogenous Bmp2 gene in chondrocytes and in osteoblasts in fracture healing was investigated by generation and analysis of chondrocyte- and osteoblast-specific Bmp2 conditional knockout (cKO) mice. The unilateral open transverse tibial fractures were created in these Bmp2 cKO mice. Bone fracture callus samples were collected and analyzed by X-ray, micro-CT, histology analyses, biomechanical testing and gene expression assays. The results demonstrated that the lack of Bmp2 expression in chondrocytes leads to a prolonged cartilage callus formation and a delayed osteogenesis initiation and progression into mineralization phase with lower biomechanical properties. In contrast, when the Bmp2 gene was deleted in osteoblasts, the mice showed no significant difference in the fracture healing process compared to control mice. These findings suggest that endogenous BMP2 expression in chondrocytes may play an essential role in cartilage callus maturation at an early stage of fracture healing. Our studies may provide important information for clinical application of BMP2.

BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

“…Taking into account the results of our in vivo study 2 weeks postoperatively, this supports the hypothesis that non-union formation is due to a reduced expression of osteogenic growth factors such as e.g. BMP-2/-4/-6/-7 during the early stage of bone healing (Mi et al, 2013;Cheng et al, 2003;Tsuij et al, 2006;Schmidmaier et al, 2002;Garcia et al, 2012;Schwabe et al, 2014). Although we do not have any data on BMP-2 release from MCM in vivo, our study demonstrates for the first time that the release of BMP-2 from MCM generates healing in a challenging non-union model.…”

“…MCM are electrolyte-coated hydroxyapatite particles that are able to bind growth factors, such as Bone Morphogenetic Protein-2 (BMP-2). Bone morphogenetic proteins have been shown to play an important role in fracture healing (Mi et al, 2013). BMP-2 is a member of the transforming growth factor-β superfamily and induces bone formation in vivo (Huang et al, 2008).…”

“…BMP-2 acts during the early stage of fracture healing by promoting differentiation of mesenchymal stem cells and osteoprogenitor cells into osteoblasts (Mi et al, 2013;Cheng et al, 2003). Numerous studies using in vitro, ex vivo and in vivo settings have investigated the molecular pathways of BMP-2, demonstrating a triggering function of osteogenesis through various autocrine and paracrine regulatory mechanisms, such as the BMP/Smad-pathway (Mi et al, 2013;Huang et al, 2008;Cheng et al, 2003;Tsuij et al, 2006;Turgemann et al, 2001;Zegzula et al, 1997;Gazit et al, 1999;Ten Dijke et al, 2006).…”

Inducible chondrocyte-specific overexpression of BMP2 in young mice results in severe aggravation of osteophyte formation in experimental OA without altering cartilage damage

“…In this process of bone formation, BMP2 plays an important role in inducing transient cartilage that is replaced by bone. This is seen in new bone formation in embryos,10 in tissue engineering11 and during fracture healing 12 13. During osteophyte formation in OA, BMP2 might be involved in a similar process 14…”

Effects of Anadara granosa shell combined with Sardinella longiceps oil on oesteoblast proliferation in bone defect healing process

“…Anadara granosa shells also contain other minerals, such as CaC (98.7%), Mg (0.05%), Na (0.9%), P (0.02%) and other elements (0.2%). 1 Similarly, a research conducted by Hafisko et al 18 showed that Anadara granosa shells contains CaCO3 that can be converted into more biocompatible hydroxyapatite compounds than calcium carbonate alone, so the process is more osteoconductive conditioned by inducing BMP-2. BMP-2 can increase the differentiation of periosteal cells, derivatives of mesenchymal stem cell (MSC) in the formation of chondroblasts and osteoblas.…”