Role of Cx43-Based Gap Junction in Murine Osteoblast-Like Mc3t3-E1Cells Exposed to 17-Βestradiol

Abstract

Estrogen has garnered considerable attention because of its importance in bone mass maintenance and the efficacy of hormone therapy in combating postmenopausal osteoporosis. Gap junctions are membrane spanning protein channels present on the surfaces of adjacent cells. They enable neighboring cells to physically link, which facilitate intercellular communication by allowing passage of small molecules from cell to cell in a process known as Gap Junctional Intercellular Communication (GJIC), can make the relevant cells function as a whole. An in vitro experiment combined with microarray analyses has identified novel genes in the response of MC3T3-E1 cells to an appropriate concentration of 17-β estradiol and the results of microarray showed that gap junction alpha-1 (Gja1) in the gap junction pathway was significantly elevated. We studied the effect of 17-β estradiol on the proliferation and differentiation of MC3T3-E1 cells disrupting of GJIC among osteoblasts with the chemical inhibitor, 18α-Glycyrrhetinic Acid (AGA). And we found that an appropriate concentration and duration of 17-β estradiol increased Methyl Thiazol Tetrazolium (MTT) values, Alkaline Phosphatase (ALP) activity and Runt-related transcription factor 2 (Runx2) proteins and gene expression and facilitated the mineralization of extracellular matrix. However, the promoting effect of 17-β estradiol on the proliferation and differentiation of MC3T3-E1 cells was weakened under the action of AGA. Therefore, we suggest that 17-β estradiol promotes MC3T3-E1's proliferation, differentiation and functions associated with Cx43-based GJIC, but gap junction is not the only signaling pathway that mediates the influence of 17-β estradiol on osteoblasts. The specific regulatory mechanism has yet to be researched.

Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy

“…We found the optimal dose of each inhibitor-25 µM of AGA for Runx2 and 10 µM of T0070907 for PPARγ. Previous studies also used the same doses of inhibitors to observe aberrant differentiation [26,30,34,35], which was consistent with our results. Over 25 µM of AGA killed more than 50% of cells due to the cytotoxicity of this inhibitor.…”

The Relationship between Renin–Angiotensin–Aldosterone System (RAAS) Activity, Osteoporosis and Estrogen Deficiency in Type 2 Diabetes

“…Furthermore, Cbfa-1 is a potent transcription factor that regulates the expression of many of the osteoblast and chondrocyte functions and triggers the expression of major osteoblastspecific lineage genes [104,105]. Angiotensin II can promote an increase in intracellular cAMP and subsequently activate signaling pathways that are involved in the control of low-density-lipoproteins (LDLs), which in turn changes Cbfa1 expression [106,107]. LDLmediated cholesterol administration improves osteoclast survival, and hence their lifespan, considerably [108,109].…”