title: Combined effects of recombinant human BMP-2 and Nell-1 on bone regeneration in rapid distraction osteogenesis of rabbit tibia.
abstract: Distraction osteogenesis (DO) has been accepted as an effective technique for bone lengthening. However, the long treatment period and possible fibrous union or nonunion hampers its further clinical application. Bone regeneration in DO involves multiple stages of repair and coordinated action of multiple cell types. Consequently, it may be possible to enhance bone regeneration through treatment strategies that target more than one repair process or cell types. The goal of this study was to determine the combined effects of recombinant human bone morephogenetic protein 2 (rhBMP-2) and NEL-like molecule-1 (NELL-1) on bone formation in DO. Unilateral tibiae in 48 rabbits were lengthened for 7days at a rate of 2mm/day after 3-day lag. At the end of distraction, the animals were randomly divided into four groups (n=12) and received phosphate-buffered saline, 50μg rhNell-1 or 50μg rhBMP-2, or both 25μg rhBMP-2 and 25μg rhNell-1 at the lengthened segment, respectively. After 4-week consolidation bony healing was assessed using histology, radiography, dual energy X-ray absorptiometry, micro-CT, and three-point bend testing. Treatment with rhNell-1 and/or rhBMP-2 resulted in better bone formation and higher BMD and BMC than the saline group, whilst excellent bone formation and the highest BMD and BMC was observed in the combined treatment group. Both rhNell-1 and rhBMP-2 groups presented more mature characteristics in the micro-architecture than the saline group, whereas the combined treatment group presented the highest BV/TV, Tb.Th and Tb.N as well as the lowest Tb.Sp. The peak load of the lengthened tibia increased by 71% in the combined treatment group, 54% in the rhBMP-2 group, and 25% in the rhNell-1 group compared to the control group, respectively. This work suggests that BMP-2 and Nell-1 enhance each other's ability and dual delivery of two agents can significantly improve bony healing in tibial DO.
authors.affiliation: The State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, Sichuan University West China College of Stomatology, Chendgu, Sichuan 610041, China.
authors.forename: Songsong
authors.initials: S
authors.lastname: Zhu
authors.forename: Donghui
authors.initials: D
authors.lastname: Song
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Jiang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002135:Calcium-Binding Proteins; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D019857:Osteogenesis, Distraction / Q000379:methods*; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D002135:Calcium-Binding Proteins; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins