1. TIMP-1 inhibits proliferation and osteogenic differentiation of hBMSCs through Wnt/β-catenin signaling
- Author
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Jianhua Ren, Kun Wang, Hui Yao, Tangzhao Liang, Lei Zhu, Dehai Shi, and Wenling Gao
- Subjects
0301 basic medicine ,Osteocalcin ,Biophysics ,Core Binding Factor Alpha 1 Subunit ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Bone Marrow ,Osteogenesis ,Humans ,RNA, Messenger ,Molecular Biology ,Transcription factor ,Wnt Signaling Pathway ,beta Catenin ,Cell Proliferation ,Gene knockdown ,Tissue Inhibitor of Metalloproteinase-1 ,biology ,Chemistry ,Activator (genetics) ,Cell growth ,Wnt signaling pathway ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Cell biology ,Up-Regulation ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Alkaline phosphatase ,Biomarkers - Abstract
The present study aimed to evaluate the effect of tissue inhibitor of metalloproteinase-1 (TIMP-1) on the proliferation and osteogenic differentiation potential of human bone marrow-derived MSCs (hBMSCs). hBMSCs with stable TIMP-1 overexpression or TIMP-1 knockdown were generated. Osteogenic differentiation was assessed by Alizarin Red S staining, alkaline phosphatase (ALP) activity and expression of specific markers. Compared with the vehicle controls, TIMP-1 knockdown significantly promoted the growth of hBMSCs. TIMP-1 knockdown up-regulated β-catenin and cyclin D1 proteins. During osteogenic differentiation, TIMP-1 knockdown elevated the deposition of calcium nodules, ALP activity and the mRNA levels of the osteogenic markers sex determining region Y-box 9 (Sox9), CCAAT-enhancer-binding protein and peroxisome proliferator-activated receptor γ. During osteogenic differentiation, TIMP-1 knockdown significantly enhanced the up-regulation of osteocalcin proteins. Meanwhile, TIMP-1 overexpression attenuated the Wnt/activator Wnt3a-induced up-regulation cyclin D1 and Runt-related transcription factor 2 (RUNX-2) (during osteogenic differentiation) proteins, while TIMP-1 knockdown restored the inhibitor Dickkopf 1-induced inhibition effect on the expression of β-catenin, cyclin D1 and RUNX-2. TIMP-1 plays a negative regulatory role in the proliferation and osteogenesis of hBMSCs, at least partially, through Wnt/β-catenin signaling.
- Published
- 2018