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Irisin improves delayed bone repair in diabetic female mice

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Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

The study was partially supported by grants from The Osaka Medical Research Foundation for Intractable Diseases to Y.T., the Cooperative Research Program (Joint usage/Research Center program) of the Institute for Frontier Life and Medical Sciences, Kyoto University, to Y.T., a JSPS KAKENHI Grant-in-Aid for Early Career Scientists (19K18480) and a Grant-in-Aid for Scientific Research (C: 21K09240) to Y.T., as well as a Grant-in-Aid for Scientific Research on Innovative Areas (15H05935, “Living in Space”)/Grant-in-Aid for Scientific Research (C:20K09514) to H.K. from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan

    Yuko Kinoshita, Yoshimasa Takafuji, Yuto Takada, Hiroki Ehara, Yuya Mizukami, Naoyuki Kawao & Hiroshi Kaji

  2. Life Science Research Institute, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan

    Katsumi Okumoto

  3. Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-Cho Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Jun-Ichiro Jo & Yasuhiko Tabata

Authors
  1. Yuko Kinoshita
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  2. Yoshimasa Takafuji
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  3. Katsumi Okumoto
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  4. Yuto Takada
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  7. Naoyuki Kawao
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  8. Jun-Ichiro Jo
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  9. Yasuhiko Tabata
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  10. Hiroshi Kaji
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Contributions

YK: investigation, formal analysis, and writing—original draft. YT: conceptualization, investigation, supervision, writing—review and editing, and funding acquisition. KO: resources and investigation. YT: investigation. HE: resources and investigation. YM: resources. NK: conceptualization. JJ: resources. YT: resources and writing—review and editing. HK: conceptualization, supervision, writing—review and editing, project administration, and funding acquisition.

Corresponding author

Correspondence to Hiroshi Kaji.

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Kinoshita, Y., Takafuji, Y., Okumoto, K. et al. Irisin improves delayed bone repair in diabetic female mice. J Bone Miner Metab 40, 735–747 (2022). https://doi.org/10.1007/s00774-022-01353-3

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  • DOI: https://doi.org/10.1007/s00774-022-01353-3

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