Effects of BMP‐2 on the osteogenic differentiation of bone marrow stem cells in fibrous dysplasia

• Published in: Oral diseases 2018-09, Vol.24 (6), p.1057-1067
• Main Authors: Um, S, Kim, HY, Seo, B‐M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; BMP‐2; BMSC; Bone dysplasia; Bone growth; Bone marrow; Bone Morphogenetic Protein 2 - pharmacology; Bone morphogenetic proteins; Calcium; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Cholecystokinin; Chromogranins - genetics; Collagen; Dentistry; Female; Fibrous dysplasia; Fibrous Dysplasia of Bone - genetics; Fibrous Dysplasia of Bone - pathology; Flow cytometry; Gene expression; GTP-Binding Protein alpha Subunits, Gs - genetics; Humans; Immunocytochemistry; Male; Mesenchymal Stem Cells - physiology; Middle Aged; Oct-4 protein; Osteocalcin; Osteogenesis; Osteogenesis - drug effects; Patients; Stem cells; Transplantation
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.12869

Objectives The purpose of this study was to evaluate the effects of BMP‐2 on bone‐grafting procedures for the treatment of fibrous dysplasia based on in vitro and in vivo experiments. Subjects and Methods Proliferation of stem cells was determined by colony‐forming assay, CCK‐8 assay and BrdU staining. OCT4 and NANOG expression was analysed by flow cytometry and immunocytochemistry. Osteogenic differentiation was assessed by measuring ALP activity, Alizarin red S staining and in vivo transplantation. Gene expression of the osteogenic markers, osteocalcin and type 1 collagen, was determined by RT‐PCR. Results FD‐BMSCs showed few calcium deposits and low ALP activity. Bone formation by transplanted FD‐BMSCs was also suppressed relative to that of normal BMSCs. However, BMP‐2 treatment enhanced osteogenic differentiation of FD‐BMSCs mixed with normal BMSCs in vitro and in vivo. Overall, BMP‐2 treatment promoted osteogenic differentiation of FD‐BMSCs mixed with normal BMSCs. Conclusions In patients with FD, stem cells in affected bone are influenced by the mutation, resulting in weak bone formation with the proliferation of immature osteogenic cells. Current treatment of FD involves surgical removal of excess bulk lesions, which can cause facial disfigurement. Our results suggest that BMP‐2 application is a good adjunctive modality to the surgical treatment of patients with FD.