New aspects of Bone Morphogenetic Protein (BMP) signaling: Coupling of osteoclast-osteoblast function and a bridge between genetics and epigenetics
Yuji Mishina, PhD. University of Michigan School of Dentistry
Previously, we reported that BMP signaling in osteoclasts plays a suppressive role in osteoclasts’ function to enhance osteoblast activities. Our recent attempts revealed that osteoclasts interact with osteoblasts in two distinct ways: osteoclasts enhance osteogenesis remotely through secretion factors and downregulate osteogenesis through direct interaction. BMP signaling negatively regulates both types of interactions. Up to now, significant efforts to understand bone metabolism have been devoted to osteoblast functions. However, our findings suggest that osteoclasts may be a center of bone coupling regulation. I will review our recent imaging data to discuss the physiological significance of osteoclast-osteoblast interactions. In the latter part of my talk, I will provide evidence for the involvement of BMP signaling in epigenetic regulation on cell fate specification of cranial neural crest cells. Single-cell RNA-seq analyses revealed several differentially expressed genes in cranial neural crest cells from the gain-of-function mutant mice for BMP signaling, which develop ectopic cartilage. One is Xist, a long non-coding RNA critical for X chromosome inactivation. We demonstrated in culture that BMP-2 can induce Xist, and gene silencing of Xist abrogates BMP-induced chondrogenesis. Taken together with in vivo genetic and pharmacologic analyses, I will discuss how BMP signaling epigenetically contributes to cell fate specification of stem cell population and craniofacial development through regulating chromatin structures.