Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells.

Francois N K Kwong, Stephen M. Richardson, Christopher H. Evans

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Bone morphogenetic proteins (BMPs) are critical growth factors in the osteogenic differentiation of progenitor cells during development in embryos and fracture repair in adults. Although recombinant BMPs are in use clinically, their clinical efficiency needs to be improved. The biological activities of BMPs are naturally regulated by extracellular binding proteins. The specific hypotheses tested in this study were as follows: the BMP inhibitor chordin is produced endogenously during the osteogenic differentiation of human mesenchymal stem cells (MSCs); and blockade of the activity of the BMP inhibitor increases the rate of osteogenic differentiation of human MSCs in vitro. METHODS: Human MSCs were derived from bone marrow from an iliac crest aspirate and from patients undergoing hip hemiarthroplasty. The MSCs were induced down the osteogenic pathway using standard osteogenic differentiation media, and expressions of BMP-2 and chordin were determined by gene expression analysis. During osteogenic differentiation, chordin knockdown was induced using RNA interference. Osteogenic differentiation was assessed by measuring the expression of alkaline phosphatase and calcium deposition. The differences in expression of osteogenic makers between groups were compared by analysis of variance, followed by Gabriel post hoc test. RESULTS: We demonstrate the expression of BMP-2 and chordin in human MSCs during osteogenic differentiation. Knockdown of chordin by RNA interference in vitro resulted in a significant increase in the expression of the osteogenic marker alkaline phosphatase and the deposition of extracellular mineral, in response to osteogenic stimulation. CONCLUSION: We conclude that endogenously produced chordin constrains the osteogenic differentiation of human MSCs. The targeting of BMP inhibitors, such as chordin, may provide a novel strategy for enhancing bone regeneration.

Original languageEnglish (US)
JournalArthritis Research & Therapy
Volume10
Issue number3
StatePublished - 2008
Externally publishedYes

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Bone Morphogenetic Proteins
Mesenchymal Stromal Cells
Bone Morphogenetic Protein 2
RNA Interference
Alkaline Phosphatase
Hemiarthroplasty
Bone Regeneration
chordin
Recombinant Proteins
Embryonic Development
Minerals
Hip
Intercellular Signaling Peptides and Proteins
Analysis of Variance
Carrier Proteins
Stem Cells
Bone Marrow
Calcium
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)

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Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells. / Kwong, Francois N K; Richardson, Stephen M.; Evans, Christopher H.

In: Arthritis Research & Therapy, Vol. 10, No. 3, 2008.

Research output: Contribution to journalArticle

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