title: Healing of fractures in osteoporotic rat mandible shown by the expression of bone morphogenetic protein-2 and tumour necrosis factor-alpha.
abstract: We studied the healing process of mandibular closed fractures in osteoporotic rats using specific antibodies to bone morphogenetic protein-2 (BMP-2) and tumour necrosis factor-alpha (TNF-alpha). We confirmed the osteoporosis in rats after oophorectomy by micro-CT, and then caused unilateral closed fractures in the mandible and monitored the healing process after 7, 14, 21, and 28 days. Data were compared simultaneously with those from a group of rats that had a sham operation. During healing of the fracture in the osteoporotic group there was a prolonged phase of endochondral ossification, with an increased number of osteoclasts (p<0.01). Expressions of BMP-2 and TNFalpha were more pronounced in the osteoporotic group and there was an increase in the number of osteoblasts and TNFalpha(+) cells compared with the normal control (p<0.01). BMP-2 was related to the differentiation of osteoblasts and the higher values of TNFalpha were correlated with the up-regulation of osteoclasts during the prolonged phase of bone turnover. We conclude that the healing of fractures in osteoporotic bone is delayed about a week compared with controls. In the healing of fractures in osteoporotic bone, there were more osteoblasts and osteoclasts but there was a predominance of osteoclasts probably induced by TNFalpha. The prolonged phase of bone turnover with osteoclast predominance in the osteoporotic group is suggestive of the cause of delay in the healing of the fracture.
authors.affiliation: Department of Oral and Maxillofacial Oncology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: A A Shahidul
authors.initials: AA
authors.lastname: Islam
authors.forename: L
authors.initials: L
authors.lastname: Rasubala
authors.forename: H
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Shiratsuchi
authors.forename: M
authors.initials: M
authors.lastname: Ohishi
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis; D002146:Bony Callus / Q000166:cytology; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D005596:Fractures, Closed / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008337:Mandibular Fractures / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D010010:Osteoclasts / Q000502:physiology; D010024:Osteoporosis / Q000150:complications / Q000503:physiopathology*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha