TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation

Transforming growth factor-beta（TGF-β）/bone morphogenetic protein（BMP） plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β（I/II） or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific.Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog（Hh）, Notch, Akt/m TOR, and mi RNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, mi RNAs are regulators, and b-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.

Induced pluripotent stem cells(iPSCs)——a new era of reprogramming

Embryonic stem cells （ESCs） derived from the early embryos possess two important characteristics：self-renewal and pluripotency,which make ESCs ideal seed cells that could be potentially utilized for curing a number of degenerative and genetic diseases clinically.However,ethical concerns and immune rejection after cell transplantation limited the clinical application of ESCs.Fortunately,the recent advances in induced pluripotent stem cell （iPSC） research have clearly shown that differentiated somatic cells from various species could be reprogrammed into pluripotent state by ectopically expressing a combination of several transcription factors,which are highly enriched in ESCs.This ground-breaking achievement could circumvent most of the limitations that ESCs faced.However,it remains challenging if the iPS cell lines,especially the human iPSCs lines,available are fully pluripotent.Therefore,it is prerequisite to establish a molecular standard to distinguish the better quality iPSCs from the inferior ones.

The 150 most important questions in cancer research and clinical oncology series: questions 86-93

Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which spark diverse thoughts,interesting communications,and potential collabora-tions among researchers all over the world.In this article,8 more questions are presented as follows.Question 86.In which circumstances is good supportive care associated with a survival advantage in patients with cancer?Question 87.Can we develop animal models to mimic immunotherapy response of cancer patients?Question 88.What are the mechanisms underlying hepatitis B virus-associated non-hepatocellular cancers?Question 89.Can we more pre-cisely target tumor metabolism by identifying individual patients who would benefit from the treatment?Question 90.What type of cranial irradiation-based prophylactic therapy combination can dramatically improve the survival of patients with extensive small-cell lung cancer?Question 91.How can postoperative radiotherapy prolong overall survival of the patients with resected pIIIA-N2 non-small cell lung cancer?Question 92.What are the key molecular events that drive oral leukoplakia or erythroplakia into oral cancer?Question 93.How could we track the chemothera-peutics-driven evolution of tumor genome in non-small cell lung cancer for more effective treatment?