title: Adverse effect of demineralized bone powder on osteogenesis of human mesenchymal stem cells.
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.
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, United States of America.
authors.forename: Zachary E
authors.initials: ZE
authors.lastname: Pflum
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, United States of America.
authors.forename: SunMi L
authors.initials: SL
authors.lastname: Palumbo
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, United States of America; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States of America. Electronic address: li@ortho.wisc.edu.
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Li
mesh_terms: D000328:Adult; D043168:Angiostatins / Q000378:metabolism; D018775:Bone Demineralization Technique; D018786:Bone Substitutes / Q000009:adverse effects*; D001842:Bone and Bones / Q000737:chemistry*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D011208:Powders
chemical_list: D018786:Bone Substitutes; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D011208:Powders; D043168:Angiostatins
keywords: Calcium; Demineralized bone powder; Mesenchymal stem cell; Osteogenesis; Phosphate