Exp Cell Res. 2013 Aug 1;319(13):1942-55.

Adverse effect of demineralized bone powder on osteogenesis of human mesenchymal stem cells.

Pflum ZE, Palumbo SL, Li WJ.

Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, United States of America.

 

Abstract

Demineralized bone powder (DBP) has been used by clinicians for years to treat bone defects. Although DBP treatment often leads to successful bone healing, a number of studies using DBP have demonstrated poor bone formation. It is known that soluble factors released from DBP modulate bone formation. We hypothesized that DBP releases or interacts with soluble factors that modulate osteogenesis of mesenchymal stem cells (MSCs). Our in vitro study demonstrated that the expression of mRNA transcripts of bone-related markers decreased in osteogenic culture of human MSCs (hMSCs) with DBP compared to that without DBP. Using a high-throughput protein array, we identified insulin-like growth factor binding protein-1, thrombospondin, and angiostatin that were found abundant in the medium cultured with DBP. Separately, we detected a significant reduction of soluble calcium and phosphate in the DBP-present medium compared to that in the DBP-absent medium, and showed that hMSC osteogenesis was regulated by the amounts of soluble calcium and phosphate in the medium. Moreover, DBP was shown to sequester soluble calcium and phosphate in the medium, thereby depleting them from interacting with hMSCs during osteogenesis. This study provides a possible explanation to an important question associated with the use of DBP in clinical treatments. Copyright © 2013 Elsevier Inc.

KEYWORDS: Calcium, Demineralized bone powder, Mesenchymal stem cell, Osteogenesis, Phosphate

PMID: 23726837

 

Supplemental Information: 

Pflum et al. investigated the effect of demineralized bone powder (DBP), commonly used to heal bone defects clinically, on adult mesenchymal stem cells (MSCs) in culture. MSCs are known to be involved in the process of bone formation termed osteogenesis. Their study results, differing from previous published findings, demonstrate that DBP adversely regulates the bone formation capacity of human MSCs, and suggest the regulation is mediated by DBP through sequestering soluble calcium and phosphate in the local environment.

In the study, Pflum et al. initially identified a number of soluble factors, including insulin-like growth factor-binding protein-1, thrombospondin, and angiostatin, abundant in cultured medium but did not find these factors played a regulatory role in reduction of MSC osteogenesis after individually analyzing their effects on osteogenesis. They then identified the depletion of soluble calcium and phosphate from culture medium is the cause of the reduction of osteogenesis. Human MSCs treated with DBP showed different phenotypes compared to those without DBP (Figure 1). Their finding is significant because it provides a possible explanation to varying outcomes of DBP treatment reported in clinical orthopedics.

This study provides laboratory-based research evidence that may allow for development of a viable approach to improve the outcome of DBP treatment. In addition, this work also demonstrates the importance of maintaining calcium and phosphate homeostasis in the local environment for bone formation.

Wan-ju li-1

Figure 1. Bright-field micrographs of human MSCs cultured with (+) or without (-) DBP.  Mineral particles appear bright and crystal-like in osteogenic culture.  A larger amount of mineral particles, an indication of bone formation in vitro,can be seen in culture treated without DBP.

 

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