Irisin improves delayed bone repair in diabetic female mice

• Published in: Journal of bone and mineral metabolism Vol. 40; no. 5; pp. 735 - 747
• Main Authors: Kinoshita, Yuko, Takafuji, Yoshimasa, Okumoto, Katsumi, Takada, Yuto, Ehara, Hiroki, Mizukami, Yuya, Kawao, Naoyuki, Jo, Jun-Ichiro, Tabata, Yasuhiko, Kaji, Hiroshi
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.09.2022; Springer Nature B.V
• Subjects: Advanced glycosylation end products; Bone healing; Bone morphogenetic protein 2; Computed tomography; Diabetes; Diabetes mellitus; Femur; Fibronectin; Gelatin; Glucose metabolism; Glycosylation; Hydrogels; Medicine; Medicine & Public Health; Metabolic Diseases; mRNA; Original Article; Orthopedics; Osteoblastogenesis; Proteolysis; Streptozocin; Gelatin hydrogel; Irisin; Bone repair; Diabetes; Osteoblasts
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s00774-022-01353-3

Introduction Irisin is a proteolytic product of fibronectin type II domain-containing 5, which is related to the improvement in glucose metabolism. Numerous studies have suggested that irisin is a crucial myokine linking muscle to bone in physiological and pathophysiological states. Materials and methods We examined the effects of local irisin administration with gelatin hydrogel sheets and intraperitoneal injection of irisin on the delayed femoral bone repair caused by streptozotocin (STZ)-induced diabetes in female mice. We analyzed the femurs of mice using quantitative computed tomography and histological analyses and then measured the mRNA levels in the damaged mouse tissues. Results Local irisin administration significantly blunted the delayed bone repair induced by STZ 10 days after a femoral bone defect was generated. Local irisin administration significantly blunted the number of Osterix-positive cells that were suppressed by STZ at the damaged site 4 days after a femoral bone defect was generated, although it did not affect the mRNA levels of chondrogenic and adipogenic genes 4 days after bone injury in the presence or absence of diabetes. On the other hand, intraperitoneal injection of irisin did not affect delayed bone repair induced by STZ 10 days after bone injury. Irisin significantly blunted the decrease in Osterix mRNA levels induced by advanced glycation end products or high-glucose conditions in ST2 cells in the presence of bone morphogenetic protein-2. Conclusions We first showed that local irisin administration with gelatin hydrogel sheets improves the delayed bone repair induced by diabetic state partially by enhancing osteoblastic differentiation.