AUTHOR=Jiang Liangjun , Sheng Kunkun , Wang Cong , Xue Deting , Pan Zhijun 

TITLE=The Effect of MMP-2 Inhibitor 1 on Osteogenesis and Angiogenesis During Bone Regeneration

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.596783

DOI=10.3389/fcell.2020.596783

ISSN=2296-634X

ABSTRACT=<p>Bone regeneration is a popular research focus around the world. Recent studies have suggested that the formation of a vascular network as well as intrinsic osteogenic ability is important for bone regeneration. Here, we show for the first time that matrix metalloproteinase (MMP) 2 inhibitor 1 (MMP2-I1) has a positive role in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) and angiogenesis of human vascular endothelial cells (HUVECs). MMP2-I1 activated the p38/mitogen-activated protein kinase signaling pathway to promote the osteogenesis of hBMSCs, and promoted the angiogenesis of HUVECs via the hypoxia-inducible factor-1α signaling pathway. We also found that MMP2-I1 enhanced bone formation using a rat tibial defect model and prevented bone loss using an ovariectomy-induced mouse model of osteoporosis. Data from the mouse model demonstrated that MMP2-I1 generated more type H vessels (CD31<sup>hi</sup>Emcn<sup>hi</sup>) when preventing bone loss. These results provide important insights into the regulatory effects of MMP2-I1 on bone regeneration.</p>