Anabolic Effects of a Novel Simvastatin Derivative on Treating Rat Bone Defects

Autor: Tien-Ching Lee, Hui-Ting Chen, I-Chun Tai, Li-Ting Kao, Ming-Hsin Hung, Chung-Hwan Chen, Yin-Chih Fu, Yan-Hsiung Wang, Chih-Ming Kao, Je-Ken Chang, Mei-Ling Ho
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Biomedicines, Vol 10, Iss 8, p 1915 (2022)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines10081915
Popis: Large bone defects may develop fracture nonunion, leading to disability and psychosocial burdens. Bone grafting with anabolic agents is a good autografting alternative. Simvastatin, as a cholesterol-lowering agent worldwide, is proven to enhance osteogenesis. Considering its dose-dependent adverse effects, we developed a simvastatin derivative, named KMUHC-01, which has bone anabolic capacity and lower cytotoxicity than simvastatin. We hypothesize that KMUHC-01 could help bone formation in bone-defect animal models. We used rat models of critical calvarial and long-bone defects to evaluate the effects of KMUHC-01 and simvastatin on biological changes at the bone defect through histology, immunohistology, and mechanical testing using three-point bending and evaluated the new bone formation microstructure through microcomputed tomography analysis. The newly formed bone microstructure at the calvarial defect site showed a significantly improved trabecular bone volume in the KMUHC-01 1-μM group compared with that in the control and simvastatin groups. The biomechanical study revealed a significantly increased maximal strength in the KMUHC-01 1-μM group compared with that in the control group. KUMHC-01, as a simvastatin derivative, showed a great anabolic effect in promoting bone defect healing. However, further studies will be conducted to prove the bioavailability and bone-forming efficacy of KMUHC-01 via systemic administration.
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