Simvastatin-hydroxyapatite coatings prevent biofilm formation and improve bone formation in implant-associated infections

Implant-associated infections(IAIs)caused by biofilm formation are the most devastating complications of orthopedic surgery.Statins have been commonly and safely used drugs for hypercholesterolemia for many years.Here,we report that simvastatin-hydroxyapatite-coated titanium alloy prevents biofilm-associated infections.The antibacterial properties of simvastatin against Staphylococcus aureus and Staphylococcus epidermidis biofilms in vitro was confirmed by crystal violet staining and live-dead bacterial staining.We developed a simvastatin-and hydroxyapatite(Sim-HA)-coated titanium alloy via electrochemical deposition.Sim-HA coatings inhibited Staphylococcus aureus biofilm formation and improved the biocompatibility of the titanium alloy.Sim-HA coatings effectively prevented Staphylococcus aureus IAI in rat femurs,as confirmed by radiological assessment and histological examination.The antibacterial effects of the Sim-HA coatings were attributed to their inhibitory effects on biofilm formation,as verified by scanning electron microscopic observations and bacterial spread plate analysis.In addition,the Sim-HA coatings enhanced osteogenesis and osteointegration,as verified by micro-CT,histological evaluation,and biomechanical pull-out tests.In summary,Sim-HA coatings are promising implant materials for protection against biofilm-associated infections.

CMTM3 suppresses bone formation and osteogenic differentiation of mesenchymal stem cells through inhibiting Erk1/2 and RUNX2 pathways

Osteoporosis,fracture,large-scale craniofacial defects and osteonecrosis are hot topics and are still underdiagnosed and undertreated in the clinic.It is urgent to understand the molecular mechanisms corresponding to the regulation of bone formation.CMTM3(CKLF-like MARVEL transmembrane domain containing 3)connects the classic chemokine to the transmembrane 4 superfamily and plays an important role in intracellular vesicles transport,EGF receptor function maintenance and cancer development.However,its expression and function in bone remain unclear.In this paper,we found that the bone volume/total volume,trabecular number,trabecular thickness and bone surface area/bone volume of Cmtm3 KO mice increased significantly,and trabecular separation and trabecular pattern factor decreased in Cmtm3 KO mice compared with WT mice by microcomputed tomography.Moreover,the bone mineral content,bone mineral density,ultimate force and stiffness were also increased in Cmtm3 KO mice.Using in vitro analysis,we showed that CMTM3 expression decreases during the differentiation of hBMSCs to osteoblasts.Knockdown of CMTM3 promoted ALP and mineralization of hBMSCs and facilitated osteoblastic differentiation with increasing RUNX2 expression.However,overexpression of CMTM3 got the opposite results.These results proved that CMTM3 was essential for osteogenic differentiation.In addition,knockdown of CMTM3 enhanced p-Erk1/2,but had no significant effect on p-Akt or p-STAT3 in hBMSCs and MC3T3-E1 cells.Taken together,our results indicated that Erk1/2 and RUNX2 pathways mediated by CMTM3 were involved in the process of osteogenic differentiation,and CMTM3 might be a new potential target in the treatment of bone formation-related disease.

Crosstalk between bone and other organs

Bone has long been considered as a silent organ that provides a reservoir of calcium and phosphorus,traditionally.Recently,further study of bone has revealed additional functions as an endocrine organ connecting systemic organs of the whole body.Communication between bone and other organs participates in most physiological and pathological events and is responsible for the maintenance of homeostasis.Here,we present an overview of the crosstalk between bone and other organs.Furthermore,we describe the factors mediating the cross-talk and review the mechanisms in the development of potential associated diseases.These connections shed new light on the pathogenesis of systemic diseases and provide novel potential targets for the treatment of systemic diseases.