TRIB3 inhibits proliferation and promotes osteogenesis in hBMSCs by regulating the ERK1/2 signaling pathway

Abstract

Osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs) is regulated by various factors, including bone morphogenetic proteins (BMPs), Notch, growth hormones and mitogen-activated protein kinases (MAPKs). Tribbles homolog 3 (TRIB3), a pseudokinase, plays an important role in cancer cells and adipocytes. However, TRIB3 function in osteogenic differentiation is unknown, although it is involved in regulating signaling pathways associated with osteogenic differentiation. Here, we found that TRIB3 was highly expressed during osteogenic differentiation in hBMSCs. Inhibition of focal adhesion kinase (FAK) or phosphatidylinositol 3-kinase (PI3K) resulted in a significant decrease in TRIB3 expression, and expression of TRIB3 was restored by increasing insulin-like growth factor-1 (IGF-1) via activating phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling. TRIB3 knock-down enhanced proliferation and decreased osteogenic differentiation at the middle stage of differentiation, and these effects were reversed by inhibiting the activation of extracellular signal-regulated kinase (ERK)-1/2. In conclusion, TRIB3 plays an important role in proliferation and osteogenic differentiation by regulating ERK1/2 activity at the middle stage of differentiation, and expression of TRIB3 is regulated by FAK in a PI3K/AKT-dependent manner.

Insulin growth factor‑1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β‑catenin pathway

“…IGF-1 is a type of growth factor that plays an important role in regulating the proliferation, differentiation and apoptosis of tissue cells ( 17 ). Previous studies have also reported that IGF-1 could regulate the proliferation, differentiation and apoptosis of BMSCs through the STAT3/Akt, ERK1/2, BMP2, PI3K/AKT signaling pathways ( 18 , 19 ). However, there are few reports on the role of Wnt/β-catenin pathway in these processes.…”

Down-regulation of TRIB3 inhibits the progression of ovarian cancer via MEK/ERK signaling pathway

“…p38 MAPK is closely associated with apoptosis and cell cycle changes in many malignant tumors. In in human bone marrow-derived mesenchymal stem cells (hBMSCs), TRIB3, regulated by FAK in a way that depends on PI3K/AKT, played an vital role in proliferation and osteogenic differentiation by modulating ERK1/2 activity at the middle stage of differentiation [ 29 ]. In renal cell carcinoma (RCC), researchers have found that high expression of TRIB3, which is induced by HIF-1α, enhanced cell proliferation, migration and invasion abilities by regulating the MAPK pathway [ 30 ].…”

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

“…However, the role of MAPKs in osteogenesis is contradictory. A recent study has demonstrated that TRIB3 influenced proliferation and differentiation in the middle stage of differentiation by inhibiting the ERK1/2 [ 44 ]. As mentioned above, the molecular mechanism that TLR4 is involved in controlling the fate of MSCs toward osteogenesis is still uncovered.…”