title: Recombinant human bone morphogenetic protein-4 (BMP-4)-stimulated cell differentiation and bone formation within the expanding calvarial suture in rats.
abstract: Suture expansion osteogenesis, which induces active bone formation within the distracted area by mechanical stress, provides an alternative form of treatment of some bone deficiency problems in craniofacial field, such as craniosynostosis, palate cleft, or narrow maxilla. However, how to stimulate new bone formation within the distracted area remains a great challenge. In this study, the effect of recombinant human bone morphogenetic protein (rhBMP-4) on bone formation induced by mechanical stimuli was investigated. The expanded midsagittal sutures of the rat calvaria were maintained in an organ culture system in the absence (control group) or presence (experimental group) of rhBMP-4 (25 or 50 ng/mL). Proliferating cell nuclear antigen, alkaline phosphatase (ALP) activity, and messenger RNA levels of core-binding factor alpha 1 (Cbfa1) and ALP were detected to determine the cell proliferation and differentiation. Bone formation within the suture was evaluated by histologic and fluorescent examination. No difference in the number of proliferating cell nuclear antigen-positive cells was found between the control and the experimental groups, whereas ALPase activity and messenger RNA levels of Cbfa1 and ALP in the experimental group were higher than that in the control group. Bone formation was accelerated in the rhBMP-4-treated group when compared with the control group. In addition, the amounts of bone formation and cell differentiation in response to 25 ng/mL of rhBMP-4 were almost equal to those induced by 50 ng/mL of rhBMP-4. Our results suggest that application of exogenous rhBMP-4 could enhance new bone formation within the rapid expanded sutures by stimulating osteoblast differentiation.
authors.affiliation: State Key Laboratory of Oral Diseases, Department of Orthodontics, Sichuan University, Chengdu, China.
authors.forename: Qingran
authors.initials: Q
authors.lastname: Shen
authors.forename: Songsong
authors.initials: S
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Ning
authors.initials: N
authors.lastname: Geng
authors.forename: Shujuan
authors.initials: S
authors.lastname: Zou
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000008:administration & dosage / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis / Q000235:genetics; D003393:Cranial Sutures / Q000187:drug effects* / Q000473:pathology; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D019857:Osteogenesis, Distraction / Q000379:methods*; D010294:Parietal Bone / Q000187:drug effects* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D013314:Stress, Mechanical; D013997:Time Factors
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D050659:Core Binding Factor Alpha 1 Subunit; D005456:Fluorescent Dyes; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000469:Alkaline Phosphatase