Regulatory Loops Consisting of Transcription Factors and Microrna Species Determine the Mineralizing Characteristics of Cell Phenotypes — Implications for Bone Engineering and Prevention of Soft Tissue Mineralization

From a literature search (PubMed) on “SP1 transcription factor and osteoblasts”, SP1 is somehow interfering with the effect of Runx2, SP7 (Osx), FIAT (inhibitor of ATF4), ETS-like TFs, MZF1 (myeloid zinc finger), JunB, and also directly affecting the transcription of marker genes like Col1α1, Col5α1, Col5α3, Col11α2, Fibromodulin, Osteocalcin, MGP (matrix-gla protein), RANKL, Pit phosphate transporter, Integrin β5, and TGFβ-R1. Furthermore, a similar search on “FosB and osteoblasts” revealed that FosB is interfering with the effect of BMPs and TGFs on the expression of downstream signaling molecules like Smads, TCF/LEF, as well as c-myc, and fra-1, but also directly modulating the transcription of IL-11 (which suppresses DIKK1 & DIKK2, thus enhancing Wnt-signaling), stimulating Pref-mediated dedifferentiation of adipocytes, relaying stretch-mediated osteoblast differentiation, counteracting the negative effect of Notch1 (a decrease in the expression of Col1α1, Osteocalcin, and ALP) by obliterating its negative effect on the Wnt/β-catenin pathway. Finally, the recent literature describes the positioning of ETS1 in the differentiation of osteoblasts in this way: Leptin is a strong inducer of osteoblast differentiation working through Stat3 (ref), and it was shown that ETS1, along with Stat1, Stat3, and VDR were induced by Calcitriol (1,25(OH) 2 D 3 ) in UMR-106 osteoblast like cells, and that ETS1 is essential for connective tissue factor (CTGF/CCN2) induction by TGF-β1 in osteoblasts, synergizing with Smad3.