Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor

Abstract

Abstract:Objective: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). Methods: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. Results: Overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialoprotein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0-and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. Conclusion: Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.

Osteoinduction by Ca-P biomaterials implanted into the muscles of mice

“…Wang et al (2004a) compared the bone-related gene expression of human primary osteogenic sarcoma cell line SaOS-2 cultured on calcium phosphate ceramics with different phase compositions and different sintering temperatures in vitro. The gene expression patterns from his and other researches supported the biocompatibility and bioactivity potentials of calcium phosphate ceramics (Wang C. et al, 2004b;Wang H. et al, 2007;Wang J.J. et al, 2009;Guo et al, 2009). Previous research on safety was mainly focused on histological analysis of long-term tissue response after the biomaterials were implanted in the animals.…”

Microarray Evaluation of Age-related Changes in Human Dental Pulp

“…CTGF is an ECM-associated signaling molecule having mitogenic and chemotactic activities that stimulate synthesis of extracellular matrix components, promoting both the growth and the differentiation of most mesenchymal cells (27). In literature, it has been documented that CTGF significantly enhances the expression of collagens, especially of collagen type III.…”

Mesenchymal stem cells: Cell therapy and regeneration potential

“…HSCs can differentiate into all of the blood and immune lineages and have been used for treating leukemia and blood disorders (Helg, Starobinski, Jeannet, & Chapuis, ). Despite the isolation of MSCs from a wide range of adult sources as well as reports of differentiation of these cells into various lineages such as adipogenic, chondrogenic, osteogenic, and neurogenic cells (Hemmingsen et al, ; Moghadam et al, ; Tropel et al, ; J. Wang et al, ), therapeutic use of MSCs has been hampered due to a number of reasons. First, isolation of MSCs from adult sources involves invasive and often painful procedures with possible donor site morbidity (Hass, Kasper, Böhm, & Jacobs, ).…”