TIMP-1 inhibits proliferation and osteogenic differentiation of hBMSCs through Wnt/β-catenin signaling. Issue 1 (8th January 2019)

• Record Type: Journal Article
• Authors: Liang, Tangzhao; Gao, Wenling; Zhu, Lei; Ren, Jianhua; Yao, Hui; Wang, Kun; Shi, Dehai
• Is Part Of: Bioscience reports. Volume 39:Issue 1(2019)
• Publication Date: 2019-01-08
• Subjects: Cell proliferation -- Mesenchymal stem cells -- Osteogenic differentiation -- Tissue inhibitor of metalloproteinase-1 -- Wnt/β-catenin signaling; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20181290
• Languages: English
• ISSNs: 0144-8463

Abstract

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.