Dermatopontin in the extracellular matrix enhances osteogenic differentiation of adipose-derived mesenchymal stem cells

Abstract

Background: Dermatopontin (DPT) is a 22-kDa tyrosine-rich extracellular matrix (ECM) protein that is found at high levels in demineralized bone matrix and cartilage and may play an important role in skeletal tissue function. In the current study, we investigate whether DPT in the ECM plays a role in the enhanced osteogenic differentiation of adipose-derived stem cells (ADSCs). Methods: In order to determine whether DPT modulates osteogenesis, we overexpressed the DPT gene in ADSC using stable lentiviral infection, induced the DPT-overexpressing cells to differentiate, and isolated the ECM secreted by these cells during osteogenesis. Using the secreted ECM with "higher than normal" levels of DPT embedded within as a substrate for cell growth, we assessed the extent to which the excess DPT modulated osteogenic marker expression during osteogenic differentiation of naive ADSC. Results: We found that ADSC cultured on the DPT-enriched ECM differentiated towards an osteogenic phenotype more robustly, as measured by expression of osteogenic marker genes. Conclusions: This may indicate an important role for DPT in the induction of stem cells toward an osteoblast phenotype during skeletal wound healing. DPT may present a novel candidate for future studies of stem cell osteogenesis and the development of more biologically relevant biomaterial substrates for bone regeneration.

Cloning, expression and purification of recombinant dermatopontin in Escherichia coli

“…Although protein was not obtained in soluble fraction, it was effectively refolded and showed activity comparable to that of standard DPT. The present study gives a promising foundation for recombinant production of DPT in prokaryotic system for its utilisation in various applications like bone tissue engineering [ 4 ], wound healing particularly for cutaneous tissue regeneration [ 5 , 6 ] and also as an effective cosmetic anti-aging formulant [ 38 ]. It has been proved to be effective as therapeutic for metabolic disorders [ 15 ] and also has been reported to be vital for ventricular remodelling after myocardial infarctions [ 35 ].…”

“…The wide range expression of this protein in different mammalian tissues, suggests that it has multiple functions. Apart from its major function in maintaining the functional tissue integrity of skin ECM architecture, it has also found to have major role in promoting cell adhesion, wound healing, osteogenic differentiation of adipose derived stem cells, and angiogenesis [4][5][6][7]. It is also known to interact with Transforming growth factor beta 1 (TGFβ1) and Decorin proteins to modulate various processes [8].…”