Endothelial Progenitor Cells Enhance the Migration and Osteoclastic Differentiation of Bone Marrow-Derived Macrophages in vitro and in a Mouse Femur Fracture Model through Talin-1

Abstract

Background/Aims: Bone resorption mediated by osteoclasts plays an important role in bone healing. Endothelial progenitor cells (EPCs) promote bone repair by stimulating neovascularization and osteogenesis. However, the role of EPCs in osteoclast formation and function is not well defined. The aim of this study was to elucidate mechanisms of EPCs in osteoclast formation and function. Methods: In this study, we examined the effects of EPCs on the proliferation, migration and osteoclastic differentiation of primary mouse bone marrow-derived macrophages (BMMs) in a co-culture system in vitro. We also evaluated the effects of EPC co-transplantation on the homing and osteoclastic differentiation of transplanted BMMs in a mouse bone fracture model in vivo. The technology of immunofluorescence, immunohistochemical, western blot, Rt-PCR, cell co-culture and Transwell were used in this study. Results: EPCs secreted TGF-β1 in the EPC-BMM co-culture medium and increased Talin-1 expression in the co-cultured BMMs. Treatment with a TGF-β1 neutralizing antibody or Talin-1 silencing in BMMs completely inhibited BMM osteoclastic differentiation in the co-culture system. These results indicated that the osteoclastogenic effects of EPCs were mediated by TGF-β1-mediated Talin-1 expression in BMMs. In the femur fracture model, BMMs co-transplanted with EPCs exhibited enhanced engraftment into the fracture site and osteoclastic differentiation compared with those transplanted alone. Mice treated with EPC-BMM co-transplantation exhibited increased neovascularization at the fracture site and accelerated fracture healing compared with those treated with BMMs alone. Conclusion: Taken together, the results suggest that EPCs can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors.

<p>Biodistribution and sensitive tracking of immune cells with plasmonic gold nanostars</p>

“…Macrophages migration towards tissues are driven by cytokines and chemokines secreted by extracellular matrix especially for the inflammatory sites 39–41. Bone marrow and the epithelial cells of vessels inside the bones can secret some of these chemotactic molecules and the homing of in vitro generated bone marrow derived macrophages to the bones has been confirmed in animal experiments 42,43. Compared to the previous experiments, our study provided a quantitative approach to show the homing of macrophage to the bones over time.…”

Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis

“…In addition, a large number of intrabone-administered MSCs should remain in the bone environment, whereas more than 90% of MSCs become trapped in the lungs and other tissues when they are infused by intravenous injection [20]. Furthermore, tibial administration, via the intra-bone marrow route, has been shown to rapidly accelerate the proliferation of donor-derived progenitor cells, even in the bone marrow of noninjected femur [21]. Therefore, intra-bone marrow administration of Sca-1-sorted MSCs may be a more focused remedy because Sca-1-sorted MSCs possess a greater potential for cell proliferation.…”

Mechanisms of action of neuropeptide Y on stem cells and its potential applications in orthopaedic disorders

“…VEGF is one of the most important components in angiogenesis, which is regarded as an essential factor that directly influences the fracture healing process[ 74 ]. BMSCs can promote vessel sprouting and vascularization, which is considered to be important for bone formation, whilst ECs can accelerate bone repair by facilitating the recruitment of osteoclast precursors and stimulating the osteoclastogenic process[ 75 ]. NPY can also facilitate vessel sprouting, adhesion, migration, proliferation, and capillary tube formation in ECs[ 10 , 59 , 65 ].…”