Bone homeostasis depends on the resorption of bone by osteoclasts and formation of bone by osteoblasts. Imbalance of this tightly coupled process can cause diseases such as osteoporosis. Thus, the mechanisms that regulate communication between osteoclasts and osteoblasts are critical to bone cell biology. It has been shown that osteoblasts and osteoclasts can communicate with each other through direct cell-cell contact, cytokines and extracellular matrix interaction. Osteoblasts can affect osteoclast formation, differentiation or apoptosis through several pathways, such as OPG/RANKL/RANK, LGR4/RANKL/RANK, Ephrin2/ephB4 and Fas/FasL pathways. Conversely, osteoclasts also influence formation of bone by osteoblasts via the d2 isoform of vacuolar (H+) ATPase (v-ATPase) V0 domain (Atp6v0d2), complement component 3a, semaphorin 4D or microRNAs. In addition, cytokine released from the resorbed bone matrix, such as TGF-β and IGF-1 also affects the activity of osteoblasts. Several reviews have been performed on the osteoblasts-osteoclasts communication. However, few reviews have shown the research advances in the recent years. In this review we summarized the current knowledge on osteoblast-osteoclast communication.

This work was supported by the grants of the National High Technology Research and Development Program of China, 863 Program No. SS2015AA020402, and the Key Projects of Military Medical Research, No. BWS11J058. There were no competing interests.

Aims: Activation of hepatic stellate cells (HSCs) plays a pivotal role at the center of the fibrogenic progression in nonalcoholic steatohepatitis (NASH). However, it is poorly understood that how various molecules interact within HSCs during the progression of NASH to fibrosis. The aim of the present study is to delineate how inflammasome molecules, hedgehog signaling and autophagy provoke HSC activation using palmitic acid (PA) as a major insult. Main methods: Inflammasome activation, hedgehog signaling activity and autophagy in PA-exposed HSCs were determined to investigate their role in activation of human and rodent HSC lines or primary HSCs. Key findings: PA treatment elicited HSC activation reflected by increased mRNA levels of transforming growth factor-β1, connective tissue growth factor, tissue inhibitor of metalloproteinase-1 and procollagen type I (α1). In addition, expression levels of NOD-like receptor protein 3 (NLRP3) and hedgehog signaling transcription factor Gli-1 were increased in PA-exposed HSCs. It's evident that PA treatment resulted in increased production of light chain 3-II and autophagosomes, as well as enhanced autophagy flux reflected by transduction of an adenoassociated viral vector. Whereas, reduced autophagy, which is often seen in the late stage of NASH, provoked inflammasome activation. Moreover, suppressing the Hh signaling pathway by LDE225 blocked production of light chain 3-II and autophagy flux. Significance: Saturated fatty acids, such as PA, stimulate HSC activation through inflammasomes and hedgehog signaling. Meanwhile, compromised autophagy may facilitate HSC activation, implicating valuable candidates for pharmacologic intervention against the progression of fibrogenesis in NASH.

BackgroundBiomarker-targeted molecular imaging holds promise for early detection of pancreatic cancer. The aim of this study was to design and evaluate a plectin-1 targeted multi-functional nanoparticle probe for pancreatic cancer imaging.Methods1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-amino(polyethylene glycol) (DSPE-PEG-NH2)-modified superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) were conjugated with plectin-1 antibody and/or Cy7 to create the multi-functional targeted nanoparticle targeted probe (Plectin-SPION-Cy7) or non-targeted probe (SPION-Cy7). Pancreatic carcinoma cell lines expressing plectin-1 were cultured with the targeted or control probes and then were imaged using confocal laser scanning microscopy and magnetic resonance imaging (MRI). Accumulations of the nanoparticles in pancreatic tumor xenografted mice were determined by MRI and fluorescence imaging.ResultsIn vitro optical imaging and MRI showed that the targeted nanoparticles were highly accumulated in MIAPaCa2 and XPA-1 carcinoma cells but not in non-carcinoma MIN6 cells, which was further confirmed by Prussian blue staining. In vivo MRI showed a significant T2 signal reduction. Prussian blue staining further confirmed that the plectin-1 targeted nanoparticles were highly accumulated in the tumor mass but not in normal pancreatic tissues, or in the liver and kidney, and few nanoparticles were observed in the tumors of mice injected with SPION-Cy7.ConclusionsOur data demonstrate that plectin-1 targeted fluorescence and MR dual-functional nanoparticle can visualize pancreatic cancer, and it has great potential to be used with various imaging devices for pancreatic cancer detection.

No abstract