title: Comparison of ectopic bone formation process induced by four calcium phosphate ceramics in mice.
abstract: Phase composition played a key role in the biodegradation of calcium phosphate ceramics (CaP), which in turn influences the osteoinductive ability. The in vivo biological mechanism is still poorly understood. In this study, four types of porous CaP ceramics were investigated, namely, hydroxyapatite (HA), β-tricalcium phosphate (TCP), and biphasic calcium phosphates BCP1 and BCP2, with HA to β-TCP ratios of 70/30 and 30/70, respectively. The four types of ceramics were implanted into thigh muscle of mice for 16weeks. Longitudinal ectopic bone formation process at gene, protein, and tissue level induced by the material was assessed. Histological analysis revealed that BCP2 was the only group that had promoted new bone formation after 16weeks. In micro-CT analysis of biodegradation, the BCP2 group had the least increment of porosity due to the new bone formation, resulting in a significant elevation in material density. Instead of a steady increase, multiple peaks were observed in most of the temporal gene expression patterns. The gene expression results were further confirmed by immunohistochemical staining of the corresponding proteins. Among the target genes, Osterix and type I collagen were activated successively. The osteoinductive BCP2 group showed earlier and significantly higher peaks in BMP2, BMPR1A, and OPG expressions than non-bone forming groups. These findings revealed that the occurrence time and magnitude of these osteogenetic gene expression peaks can be crucial in the osteoinduction process.
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Zhurong
authors: Z
authors: Tang
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Yanfei
authors: Y
authors: Tan
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Yilu
authors: Y
authors: Ni
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Jing
authors: J
authors: Wang
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Xiangdong
authors: X
authors: Zhu
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Yujiang
authors: Y
authors: Fan
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors: Xuening
authors: X
authors: Chen
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China. Electronic address: xiaoyang114@scu.edu.cn.
authors: Xiao
authors: X
authors: Yang
authors: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China. Electronic address: zhangxd@scu.edu.cn.
authors: Xingdong
authors: X
authors: Zhang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology*; D002516:Ceramics / Q000494:pharmacology*; D002828:Choristoma / Q000473:pathology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D020007:Implants, Experimental; D008297:Male; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D016062:Porosity; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014961:X-Ray Diffraction; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D024042:Collagen Type I; D053244:Osteoprotegerin; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: BMP2; Calcium phosphate ceramics; Osteoinduction; Phase composition