Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor‐promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor‐promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor‐promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC‐conditioned media (MSC‐CM) showed that MSC‐CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial‐mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC‐CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N‐cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN‐mediated PI3K/Akt/mTOR activation.

Background and Purpose: Melatonin is a neurohormone involved in bone homeostasis. Melatonin directs bone remodelling and the role of bone marrow mesenchymal stem cells (BMMSCs) in the regulating melatonin-mediated bone formationresorption balance remains undefined. Experimental Approach: Osteoporosis models were established and bone tissue and serum were collected to test the effects of melatonin on bone homeostasis. Melatonin receptors were knocked down, the NF-κB signalling pathway and receptor activator of NF-κB ligand (RANKL) expression were investigated. Communication between bone marrow mesenchymal stem cells and osteoclasts was detected with directcontact or indirect-contact system. Key Results: Bone loss and microstructure disorder in mice were reversed after melatonin treatment, as a result of anabolic and anti-resorptive effects. In vitro, a physiological (low) concentration of melatonin promoted the bone marrow mesenchymal stem cells, osteogenic lineage commitment and extracellular mineralization but had no impact on extracellular matrix synthesis. After MT knockdown, especially MT 2 , the positive effects of melatonin on osteogenesis were attenuated. The canonical NF-κB signalling pathway was the first discovered downstream signalling pathway after MT receptor activation and was found to be down-regulated by melatonin during osteogenesis. Melatonin suppressed BMMSC-mediated osteoclastogenesis by inhibiting RANKL production in BMMSCs and this effect only occurred when BMMSCs and osteoclast precursors were co-cultured in an indirect-contact manner. Conclusion and Implications: Our work suggests that melatonin plays a crucial role in bone balance, significantly accelerates the osteogenic differentiation of bone marrow mesenchymal stem cells by suppressing the MT 2 -dependent NF-κB signalling pathway, and down-regulates osteoclastogenesis via RANKL paracrine secretion. Abbreviations: ALP, alkaline phosphatase; BMD, bone mineral density; BMMs, bone marrow monocytes; BMMSCs, bone marrow mesenchymal stem cells; BV/TV, trabecular bone volume per total volume; Col-I, collagen I; CTX-I, C-terminal telopeptide α1 chain of type I collagen; H&E, haematoxylin and eosin; Mel, melatonin; OCN, osteocalcin; OPG, osteoprotegerin; OVX, ovariectomy; PINP, N-terminal propeptide of type I procollagen; RANK, receptor activator of NF-κB; RANKL, receptor activator of NF-κB ligand; TRAP, tartrate-resistant acid phosphatase; Tb. N, trabecular bone number; Tb. Sp, trabecular bone separation; Tb. Th, trabecular bone thickness; μCT, micro-CT.

Resulting from their versatile functionality, nanomaterials with low systemic toxicity have offered high-performance diagnostic and therapeutic capabilities. Here, we designed and synthesized uniform magnesium silicate hollow spheres as high drug-loading nanocarriers for cancer therapy. Through a classical Stöber method and a hydrothermal process, well-defined MgSiO3 hollow spheres were prepared in a facile route with inexpensive inhesion. Compared with routinely used mesoporous silica nanoparticles, our MgSiO3 hollow spheres with larger void space and mesoporous shell endowed the structures with a much higher storage capacity of guest molecules (2140 mg DOX g(-1)) and a much more sustained release of anticancer drugs. In detail, the release property and therapeutic efficacy of DOX-loaded nanoparticles were evaluated in vitro and in vivo. In vitro experiments revealed that these nanoparticles were mostly accumulated in lysosome, which facilitated continual drug release and efficient cancer cell destruction. We further demonstrated that these DOX-loaded nanoparticles could effectively suppress tumor growth compared to free DOX in vivo, as DOX-loaded-nanoparticle-treated mice survived over 15 days without obvious detectable tumor growth. Otherwise, long-term toxicity study was also evaluated, indicating their overall safety and great potential in biomedical applications.

Hierarchical hybrid micro-/nanostructured titanium surface has a favorable biocompatibility, which can promote osteoblast differentiation. It could possibly accelerate bone growth, promote bone formation at early stage, and guarantee the immediate loading and early stage loading in clinical practice.