Background: Forkhead box protein f1 (Foxf1) is associated with cell differentiation, and may be a key player in bone homoeostasis. However, the effect of Foxf1 on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) and ovariectomy-induced bone loss, as well as its clinical implications, is unknown. Methods: By quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blotting, we assayed Foxf1 expression in bone tissue, BMSCs, and bone marrow-derived macrophages (BMMs), derived from ovariectomised (OVX) mice, and during osteogenic differentiation and osteoclast differentiation. Using a loss-of-function approach (small interfering RNA [siRNA]-mediated knockdown) in vitro, we examined whether Foxf1 regulates osteoblast differentiation of BMSCs via the Wnt/b-catenin signalling pathway. Furthermore, we assessed the anabolic effect of Foxf1 knockdown (siFoxf1) in OVX mice in vivo. We also assayed the expression of Foxf1 in bone tissue derived from postmenopausal osteoporosis (PMOP) patients and its link with bone mineral density (BMD). Finally, we examined the effect of Foxf1 knockdown on the osteoblastic differentiation of human BMSCs. Findings: Foxf1 expression was significantly increased in bone extract and BMSCs from OVX mice and gradually decreased during osteoblastic differentiation of BMSCs but did not differ significantly in OVX mousederived BMMs or during osteoclast differentiation. In vitro, Foxf1 knockdown markedly increased the expression of osteoblast specific genes, alkaline phosphatase (ALP) activity, and mineralisation. Moreover, siFoxf1 activated the Wnt/b-catenin signalling pathway. The siFoxf1-induced increase in osteogenic differentiation was partly rescued by inhibitor of Wnt signalling (DKK1). In OVX mice, Foxf1 siRNA significantly reduced bone loss by enhancing bone formation. Foxf1 expression levels negatively correlated with reduced bone mass and bone formation in bone tissue from PMOP patients. Finally, Foxf1 knockdown significantly promoted osteogenesis by human BMSCs. Interpretation: Our findings indicate that Foxf1 knockdown promotes BMSC osteogenesis and prevents OVXinduced bone loss. Therefore, Foxf1 has potential as a biomarker of osteogenesis and may be a therapeutic target for PMOP.

In this paper, a series of nanostructured CeO 2 spheres with two different dopants, Co 2+ and Ni 2+ , were synthesized by a one-step hydrothermal synthesis free from the template-assisted calcination, and were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), inductively coupled plasma mass spectrometry (ICP-MS) and nitrogen adsorption-desorption measurements. The formation process of the produced spheres involved Ostwald ripening, secondary nucleation and oriented attachment. Both the presence of Co 2+ , Ni 2+ and the interaction of Ce 4+ /Ce 3+ with dopants promoted the production of oxygen vacancies, which explained the result that the catalytic performance in CO oxidation of CeO 2 with both dopants was better than that with single dopant, and that with single dopant held much advantage towards pure CeO 2 .

Autophagy takes part in regulating the eukaryotic cells function and the progression of numerous diseases, but its clinical utility has not been fully developed yet. Recently, mounting evidences highlight an important correlation between autophagy and bone homeostasis, mediated by osteoclasts, osteocytes, bone marrow mesenchymal stem cells, and osteoblasts, and autophagy plays a vital role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). The combinations of autophagy activators/inhibitors with anti-GIOP first-line drugs or some new autophagy-based manipulators, such as regulation of B cell lymphoma 2 family proteins and caspase-dependent clearance of autophagy-related gene proteins, are likely to be the promising approaches for GIOP clinical treatments. In view of the important role of autophagy in the pathogenesis of GIOP, here we review the potential mechanisms about the impacts of autophagy in GIOP and its association with GIOP therapy.

In many fields, nanoparticles are frequently dispersed onto kinds of nanocarriers integrated into hybrid nanocomposites to acquire advanced performance. However, the nanoparticles usually tend to agglomerate on the surface, according to traditional synthetic methods. Besides, the exposed state of loaded nanoparticles and the weak adhesion with the supporters make them fall off during practical application, leading to “second agglomeration” of the nanoparticles and attenuated synergistic effects. In this work, we engineered layered bimetallic (Ni–Co) hydroxides (NCHs) into enclosed nanocages derived from metal organic frameworks (MOFs). Zinc hydroxystannate (ZHS) nanoparticles were selected to be confined dispersed within the hollow cavity of the three-dimensional nanocages. ZHS nanoparticles were tightly immobilized, monodispersing to form a novel multiyolk@shell nanostructure with NCH nanocages. To prove the effectiveness of this structural design, the as-synthesized hybrids ZHS@NCH were introduced into the epoxy matrix to inquiry its performance. Compared to neat ZHS, neat NCH, and physical mixture of ZHS and NCH, ZHS@NCH conferred better flame retardancy, thermal stability, and mechanical properties upon the epoxy nanocomposites. With the adding amount of 6 wt % ZHS@NCH, the UL-94 rating of the nanocomposite was V-0, and the peak of heat release rate value was reduced by 69.1%, while the mechanical properties were slightly influenced. The ingenious synthetic strategy gives insights into uniform distribution of nanoparticles within nanocapsules and enlightens the facile fabrication of multiyolk@shell nanomaterials.

No abstract

No abstract

The mechanistic target of rapamycin (mTOR) plays a key role in sensing and integrating large amounts of environmental cues to regulate organismal growth, homeostasis, and many major cellular processes. Recently, mounting evidences highlight its roles in regulating bone homeostasis, which sheds light on the pathogenesis of osteoporosis. The activation/inhibition of mTOR signaling is reported to positively/negatively regulate bone marrow mesenchymal stem cells (BMSCs)/osteoblasts-mediated bone formation, adipogenic differentiation, osteocytes homeostasis, and osteoclasts-mediated bone resorption, which result in the changes of bone homeostasis, thereby resulting in or protect against osteoporosis. Given the likely importance of mTOR signaling in the pathogenesis of osteoporosis, here we discuss the detailed mechanisms in mTOR machinery and its association with osteoporosis therapy.

No abstract