From Cell Biology to Tissue Engineering


Effect of short-term betamethasone administration on the regeneration process of tissue-engineered bone

Takahiro Chihara1,2, Yiming Zhang1,3, Xianqi Li1,2,4, Atsushi Shinohara1,2,5 and Hideaki Kagami1,4,6

1Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, 2Department of Oral and Maxillofacial Surgery, School of Dentistry, Matsumoto Dental University, Shiojiri, Japan, 3Tenth People's Hospital, Tongji University, Shanghai, China, 4Institute for Oral Science, Matsumoto Dental University, Shiojiri, 5Midorigaoka Dental Clinic, Toyota and 6Department of General Medicine, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Offprint requests to: Hideaki Kagami, D.D.S., Ph.D., The Institute of Oral Science, Matsumoto Dental University, 1780 Hirooka Gobara, Shiojiri 399-0781, Nagano, Japan. e-mail: hideaki.kagami@mdu.ac.jp

Summary. Local inflammation at the transplanted site of tissue-engineered bone may cause apoptosis of the transplanted cells, thus negatively affecting bone regeneration. To maximize the efficacy of bone tissue engineering, the local effect of short-term corticosteroid administration at the transplanted site of tissue-engineered bone was studied with respect to the expression of inflammatory cytokines. Compact bone-derived cells from mouse leg bones were isolated, cultured and seeded onto β-tricalcium phosphate granules. The constructs were transplanted to the back of syngeneic mice. Betamethasone sodium phosphate was administered intraperitoneally to an experimental (betamethasone) group, whereas the same amount of saline was administered to a control group. When betamethasone was administered three times (immediately after operation and 12 hours and 24 hours after transplantation), the number of SP7/osterix-positive osteoblasts was larger in the betamethasone group. Three times of betamethasone administration (immediately after operation and 12 hours and 24 hours after transplantation) did not change the number of apoptotic cells and osteoclasts, but showed a slight upregulation of IL-4 and a downregulation of IL-6. However, 7 doses of betamethasone administration (over 7 consecutive days) increased the number of apoptotic cells and osteoclasts, which was correlated with a downregulation of IL-4 and an upregulation of IL-6. TNF-α expression levels showed no significant differences between the two groups. The results showed beneficial effects of 3 betamethasone administrations for bone regeneration therapy but contrary effects when betamethasone was administered 7 times due to the downregulation of anti-inflammatory cytokines (IL-4) and the upregulation of inflammatory cytokines (IL-6). As a conclusion, our results suggested the importance of the cautious usage of corticosteroids to control local inflammation at transplanted sites in bone tissue engineering. Histol Histopathol 35, 709-717 (2020)

Key words: Cortical bone-derived cells, Mesenchymal stem cells, Corticosteroid, Betamethasone, Bone tissue engineering, Local inflammation

DOI: 10.14670/HH-18-193