CXCL chemokines-mediated communication between macrophages and BMSCs on titanium surface promotes osteogenesis via the actin cytoskeleton pathway.

The refined functional cell subtypes in the immune microenvironment of specific titanium (Ti) surface and their collaborative role in promoting bone marrow mesenchymal stem cells (BMSCs) driven bone integration need to be comprehensively characterized. This study employed a simplified co-culture system to investigate the dynamic, temporal crosstalk between macrophages and BMSCs on the Ti surface. The M2-like sub-phenotype of macrophages, characterized by secretion of CXCL chemokines, emerges as a crucial mediator for promoting BMSC osteogenic differentiation and bone integration in the Ti surface microenvironment. Importantly, these two cells maintain their distinct functional phenotypes through a mutually regulatory interplay. The secretion of CXCL3, CXCL6, and CXCL14 by M2-like macrophages plays a pivotal role. The process activates CXCR2 and CCR1 receptors, triggering downstream regulatory effects on the actin cytoskeleton pathway within BMSCs, ultimately fostering osteogenic differentiation. Reciprocally, BMSCs secrete pleiotrophin (PTN), a key player in regulating macrophage differentiation. This secretion maintains the M2-like phenotype via the Sdc3 receptor-mediated cell adhesion molecules pathway. Our findings provide a novel insight into the intricate communication and mutual regulatory mechanisms operating between BMSCs and macrophages on the Ti surface, highlight specific molecular events governing cell-cell interactions in the osteointegration, inform the surface design of orthopedic implants, and advance our understanding of osteointegration.

A novel implant surface modification mode of Fe3O4-containing TiO2 nanorods with sinusoidal electromagnetic field for osteoblastogenesis and angiogenesis.

Implants made of Ti and its alloys are widely utilized in orthopaedic surgeries. However, insufficient osseointegration of the implants often causes complications such as aseptic loosening. Our previous research discovered that disordered titanium dioxide nanorods (TNrs) had satisfactory antibacterial properties and biocompatibility, but TNrs harmed angiogenic differentiation, which might retarded the osseointegration process of the implants. Magnetic nanomaterials have a certain potential in promoting osseointegration, electromagnetic fields within a specific frequency and intensity range can facilitate angiogenic and osteogenic differentiation. Therefore, this study used Fe3O4 to endow magnetism to TNrs and explored the regulation effects of Ti, TNrs, and Fe3O4-TNrs under 1 â€‹mT 15 â€‹Hz sinusoidal electromagnetic field (SEMF) on osteoblastogenesis, osseointegration, angiogenesis, and its mechanism. We discovered that after the addition of SEMF treatment to VR-EPCs cultured on Fe3O4-TNrs, the calcineurin/NFAT signaling pathway was activated, which then reversed the inhibitory effect of Fe3O4-TNrs on angiogenesis. Besides, Fe3O4-TNrs with SEMF enhanced osteogenic differentiation and osseointegration. Therefore, the implant modification mode of Fe3O4-TNrs with the addition of SEMF could more comprehensively promote osseointegration and provided a new idea for the modification of implants.

Inhibition of FAAH suppresses RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss partially through repressing the IL17 pathway.

Fatty amide hydrolase (FAAH) is a key degradation enzyme of the endocannabinoid system, mainly responsible for the hydrolysis of arachidonic acid ethanolamine (AEA). Previous investigations have shown that FAAH is involved in a series of biological processes, such as inflammation, immune regulation, and transmembrane signal transduction of neurons. Endogenous cannabinoids and cannabinoid receptors have been reported to participate in the regulation of bone homeostasis by regulating the differentiation of osteoblasts and osteoclasts. We hypothesized that FAAH may play an important role in osteoclastogenesis based on the above evidence. The present study found that the FAAH expression was increased at both mRNA and protein levels during RANKL-induced osteoclastogenesis. Pharmacological and genetic inhibition of FAAH in bone marrow-derived macrophages (BMMs) inhibited osteoclastogenesis, F-actin ring formation, bone resorption, and osteoclast-specific gene expression in vitro. Moreover, intragastric administration of the FAAH inhibitor PF-04457845(PF) ameliorated ovariectomy (OVX)-induced bone loss in mice. Further investigation revealed that nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were inhibited by PF treatment and FAAH knockdown. RNAseq indicated that the IL17 pathway was blocked by PF, and administration of recombinant murine IL17 protein could partially restore osteoclastogenesis and activate NF-κB and MAPK pathways. To sum up, our findings demonstrate that targeting FAAH could be a promising candidate strategy for treating osteoclast-related diseases, especially osteoporosis.

Reduction, mineralization, and magnetic removal of chromium from soil by using a natural mineral composite.

Reductive immobilization has been a commonly used technique to detoxify Cr(VI) from soil; however, it's challenging to remove the reduced Cr from soil to prevent its re-oxidation. This work explored a natural magnetic composite for the remediation, mineralization, and magnetic removal of Cr(VI) from the soil. It consists of 77% magnetite and 23% pyrrhotite with strong magnetic properties. A series of characterization tests show that composites of magnetite and pyrrhotite are interlaced and closely bonded, and contain no other heavy metals. The Cr(VI) removal rate increases with the decrease in composite particle size. A kinetics study shows that removing Cr(VI) by the composite is likely through both adsorption and reduction. Acidic conditions are more favorable for the immobilization of Cr(VI), at 45.8 mg Cr(VI) removal per g of composite at pH 2. After 100 days of in-situ treatment by the composite, the leaching concentration (TCLP) of Cr(VI)-contaminated soil was 1.95 mg L-1, which was below the EPA limit (5 mg L-1) for hazardous waste. After reduction, the composite was separated from soil by magnetic characteristics, and 58.2% of Cr was found mineralized. The post-treatment Cr-containing composite was analyzed by SEM-EDS, Raman spectra, and XPS. It was found that Cr was mineralized on the surface of the composite in the form of Cr(OH)3, Cr2O3, and FeCr2O4. This indicates that reduction and mineralization of Cr(VI) in the soil can be accomplished through natural magnetic mineral composites and easily separated and removed from the soil, achieving a complete soil cleanup.

The role of Ca2+ /Calcineurin/NFAT signalling pathway in osteoblastogenesis.

The bone remodelling process is closely related to bone health. Osteoblasts and osteoclasts participate in the bone remodelling process under the regulation of various factors inside and outside. Excessive activation of osteoclasts or lack of function of osteoblasts will cause occurrence and development of multiple bone-related diseases. Ca2+ /Calcineurin/NFAT signalling pathway regulates the growth and development of many types of cells, such as cardiomyocyte differentiation, angiogenesis, chondrogenesis, myogenesis, bone development and regeneration, etc. Some evidences indicate that this signalling pathway plays an extremely important role in bone formation and bone pathophysiologic changes. This review discusses the role of Ca2+ /Calcineurin/NFAT signalling pathway in the process of osteogenic differentiation, as well as the influence of regulating each component in this signalling pathway on the differentiation and function of osteoblasts, whereby the relationship between Ca2+ /Calcineurin/NFAT signalling pathway and osteoblastogenesis could be deeper understood.