Declining histone acetyltransferase GCN5 represses BMSC‐mediated angiogenesis during osteoporosis

Abstract

Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs. GCN5 promoted BMSC-mediated angiogenesis by enhancing H3K9ac levels on the promoter of The decrease of GCN5 in osteoporotic BMSCs led to the decline of proangiogenic capacity. Accordingly, overexpression of GCN5 enhanced the proangiogenic potency of osteoporotic BMSCs. Furthermore, recovering GCN5 expression by lentiviral expression vector significantly attenuated the loss of angiogenesis in ovariectomized mouse femurs. Our study results revealed an epigenetic mechanism controlling BMSC-mediated angiogenesis and provided a novel therapeutic target for osteoporosis treatment.-Jing, H., Liao, L., Su, X., Shuai, Y. Zhang, X., Deng, Z., Jin, Y. Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis.

The lysine acetyltransferase GCN5 contributes to human papillomavirus oncoprotein E7‐induced cell proliferation via up‐regulating E2F1

“…GCN5 promotes transcription by acetylating lysines 9, 14, 27 and 56 of histone H3 and lysines 8 and 16 of histone H4 . GCN5 promoted bone marrow‐derived mesenchymal stem cells (BMSCs)‐mediated angiogenesis by elevating H3K9ac levels on the promoter of VEGF . Overexpression of GCN5 promoted the growth of multiple lung cancer cell lines and facilitated the G1/S transition by acetylating histone 3 and histone 4 in the promoter of E2F1, Cyclin E1 and Cyclin D1 .…”

“…20,21,26,27 GCN5 promoted bone marrow-derived mesenchymal stem cells (BMSCs)-mediated angiogenesis by elevating H3K9ac levels on the promoter of VEGF. 55 Overexpression of GCN5 promoted the growth of multiple lung cancer cell lines and facilitated the G1/S transition by acetylating histone 3 and histone 4 in the promoter of E2F1, Cyclin E1 and Cyclin D1. 22 So far, there are no reports of GCN5 related to HPV and HPV-associated cancers.…”

LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells

“…New blood vessel formation is necessary for skeletal development during the embryonic stage, postnatal growth, and bone remodeling [6]. Recently, it has been reported that the relative abundance of the H-type vessels is important in the processes of bone formation or bone loss [7, 10].…”

“…Angiogenesis refers to the process by which new blood vessels sprout from the existing vasculature through the recruitment of endothelial cells (ECs), while vasculogenesis refers to the de novo formation of blood vessels from endothelial progenitors circulating bone marrow-derived endothelial progenitor cells (EPCs) [4, 5]. Recently, a number of breakthrough studies have pointed out that the processes of angiogenesis and osteogenesis are coupled temporally and spatially through the communication among vascular ECs, bone-building osteoblasts (OBs), and bone-resorbing osteoclasts (OCs) during bone development and remodeling [6-8]. The coupling relationship between angiogenesis and osteogenesis was reported in early studies by Clemens et al, who demonstrated that HIF-1 was a key molecule that couples angiogenesis to bone formation [9].…”

ERK1/2 and Akt phosphorylation were essential for MGF E peptide regulating cell morphology and mobility but not proangiogenic capacity of BMSCs under severe hypoxia

“…Bone marrow‐derived mesenchymal stem cells (BMSCs) are always served as reserves for bone tissue regeneration widely due to their self‐renewal ability and multiple differentiation potential, especially osteogenic potential . Besides, BMSCs have been revealed as the regulator of angiogenesis and inflammatory through secreting varies of growth factors or cytokines. Thus, BMSCs are always considered as a source of osteoblast progenitor and play an important role in bone regeneration and remodelling collaborating with functionalized scaffolds.…”