Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

Abstract

Enhanced BMP or canonical Wnt (cWnt) signaling are therapeutic strategies employed to enhance bone formation and fracture repair, but the mechanisms each pathway utilizes to specify cell fate of bone-forming osteoblasts remain poorly understood. Among all BMPs expressed in bone, we find that singular deficiency of Bmp2 blocks the ability of cWnt signaling to specify osteoblasts from limb bud or bone marrow progenitors. When exposed to cWnts, Bmp2-deficient cells fail to progress through the Runx2/ Osx1 checkpoint and thus do not upregulate multiple genes controlling mineral metabolism in osteoblasts. Cells lacking Bmp2 after induction of Osx1 differentiate normally in response to cWnts, suggesting that pre-Osx1+ osteoprogenitors are an essential source and a target of BMP2. Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) as a transcription factor in the osteoblast gene regulatory network induced during bone development and bone repair, which acts upstream of Osx1 in a BMP2-dependent manner. The Runx2/Osx1 transition therefore receives crucial regulatory inputs from BMP2 that are not compensated for by cWnt signaling, and this is mediated at least in part by induction and activation of Grhl3.

Potential Biomarkers for Primary Open-Angle Glaucoma Identified by Long Noncoding RNA Profiling in the Aqueous Humor

“…65 Moreover, BMP2 deficiency could block the ability of the WNT signaling pathway to promote osteogenesis. 66 Thus, although it is still necessary to investigate mechanistic links of ENST00000607393 expression and glaucoma, it is possible that ENST00000607393 knockdown might exert its action through the Wnt signaling pathway.…”

PTH coatings on titanium surfaces improved osteogenic integration by increasing expression levels of BMP-2/Runx2/Osterix

“…43 What is more, when BMP-2 is decient, cells fail to active Runx2/Osterix axis and osteoblastic differentiation decreases. 44 It demonstrated PTH might regulate BMP-2 signal pathway to affect bone formation, mineralization and osseointegration.…”

The lncRNA Rhno1/miR-6979-5p/BMP2 Axis Modulates Osteoblast Differentiation

“…we combined the results of the above three databases to enhance the strength of the evidence, and in order to show the process of the method of selecting target gene more clearly, we produced a Venn diagram and as shown in Figure 3A, three candidate genes were identified of interest -PI3KR1, BMP2, and LRP5. Following a literature review, although LRP5 is involved in Wnt/LRP5/β-Catenin signaling pathway, and thereby mediate the osteoblast differentiation process [22], BMP2 is a osteogenic mediator demonstrated widely in much more previous researches [23][24][25]. Thus, we select BMP2 from the three candidates as a target gene for miR-6979-5p.…”