TAZ promotes osteogenic differentiation of mesenchymal stem cells line C3H10T1/2, murine multi-lineage cells lines C2C12, and MEFs induced by BMP9

Abstract

Bone morphogenetic protein 9 (BMP9), also named as growth differentiation factor 2 (GDF-2), is the strongest cytokine that promotes osteogenic differentiation in the BMP family, and has broad clinical application value. Nevertheless, the mechanism of BMP9 promotes osteogenic differentiation remain unclear. TAZ, a transcriptional co-activator, has great effects on cell proliferation, differentiation, and stem cell self-renewal. In this research, we investigated the effects of TAZ in BMP9-induced osteogenic differentiation of mesenchymal stem cell line C3H10T1/2 (MSCs) and murine multi-lineage cell lines C2C12 and MEFs (MMCs) and explored its possible mechanisms. This study has found that BMP9 induces the expression of TAZ and promotes its nuclear translocation. Meanwhile, our study found that Ad-TAZ and TM-25659, a TAZ agonist, can enhance the osteogenic differentiation of MSCs and MMCs induced by BMP9. Conversely, Ad-si-TAZ and verteporfin, an inhibitor of TAZ, have the contradictory effect. Likewise, the promotion of TAZ to the BMP9-induced ectopic bone formation in vivo was confirmed by the subcutaneous transplantation of MSCs in nude mice. Furthermore, we have detected that TAZ might increase the levels of the phosphorylation of Smad1/5/8, p38, ERK1/2, and JNK induced by BMP9. Additionally, we also found that TAZ increased the total protein level of β-catenin induced by BMP9. In summary, our results strongly indicated that TAZ will promote the osteogenic differentiation in MSCs and MMCs induced by BMP9 through multiple signal pathways.

TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway

“…In fact, as mentioned above, the regulatory effects of TAZ on cell osteogenic differentiation are controversial. Although a considerable portion of research suggests that TAZ is a positive regulator of osteogenesis [8,9], several studies have shown that TAZ may inhibit the osteogenic process to some extent. For instance, TAZ/YAP were shown to suppress canonical Wnt signaling and Runx2 activity in mouse osteoblast progenitors and thus opposed differentiation toward the osteoblast lineage [11].…”

“…Several studies have shown that TAZ/YAP have positive effects on the osteogenic differentiation abilities of stem cells. For example, Huang reported that the nuclear translocation of TAZ determined the promotion effects of cytokine Bone morphogenetic protein 9 on osteogenic differentiation of mesenchymal stem cell line C3H10T1/2 [8]; additionally, a hyaluronan-based gel promoted human dental pulp stem cell bone differentiation by activating the TAZ/YAP Pathway [9]. However, a few studies have shown that TAZ/YAP may have detrimental effects on the osteogenic differentiation of stem cells or osteoblasts [10,11].…”

Deciphering the Role of the MST1/2-YAP Axis in Irisin-Treated Aplastic Anemia: Implications for Mesenchymal Stem Cell Function

“…In the Rotenone group, a concentration of 100 nM of the sh poison Rotenone (Rotenone, MCE, HY-B1756) dissolved in DMSO was added to the differentiation induction medium to be co-treated with BMSCs. VP + Rotenone group incorporated VP and Rotenone into the differentiation-inducing culture medium to cotreat with BMSCs [41,42,43].…”