1. Effects of Losartan and Fisetin on Microfracture-Mediated Cartilage Repair of Ankle Cartilage in a Rabbit Model.
- Author
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Stake IK, Gao X, Huard M, Fukase N, Ruzbarsky JJ, Ravuri S, Layne JE, Philippon MJ, Clanton TO, and Huard J
- Subjects
- Animals, Rabbits, Female, Disease Models, Animal, Ankle Joint surgery, Losartan pharmacology, Flavonols pharmacology, Flavonoids pharmacology, Cartilage, Articular drug effects, Cartilage, Articular surgery, Cartilage, Articular injuries
- Abstract
Background: Microfracture is one surgical treatment strategy for osteochondral lesions of the talus (OLTs) but results in fibrocartilage repair tissue, which has inferior mechanical properties to native hyaline cartilage. Biological regulation of microfracture has been suggested to improve the quality of cartilage repair in patients., Purpose: To determine if administration of losartan, fisetin, or losartan and fisetin combined can enhance microfracture-mediated cartilage repair of OLTs in a rabbit model., Study Design: Controlled laboratory study., Methods: Four-month-old female rabbits were divided into the following groups (8 rabbits per group): microfracture only (microfracture), microfracture plus losartan (losartan), microfracture plus fisetin (fisetin), and microfracture plus losartan and fisetin (losartan+fisetin). A 2.7-mm osteochondral defect and 4 microfracture holes were created in the talar dome cartilage. The rabbits were administered losartan (10 mg/kg/day), fisetin (20 mg/kg/day), or losartan and fisetin orally until euthanized 12 weeks after surgery. Gross evaluation, micro-computed tomography, histology, and immunohistochemistry evaluations of the osteochondral defects were performed as well as quantitative polymerase chain reaction of capsule tissue and enzyme-linked immunosorbent assay of serum., Results: The losartan and fisetin groups had increased International Cartilage Regeneration & Joint Preservation Society macroscopic scores with improved cartilage repair and enhanced subchondral bone healing compared with the microfracture group. However, the losartan+fisetin group did not show a synergistic effect. O'Driscoll histology scores were higher in the losartan and fisetin groups compared with the microfracture group, while the losartan+fisetin group had a lower score than the losartan, fisetin, and microfracture groups. Collagen type 2 staining revealed organized chondrocytes in the losartan and fisetin groups, but the losartan+fisetin group did not show improvement when compared with other groups. Fisetin treatment decreased catalase and transforming growth factor-β1-activated kinase 1 expression in capsular tissue., Conclusion: Concomitant microfracture and biological regulation, using oral administration of either losartan or fisetin, may improve cartilage healing of OLTs; however, losartan and fisetin combined in the current drug administration regimen does not appear to provide synergistic effects., Clinical Relevance: Oral intake of losartan or fisetin may result in beneficial effects on microfracture-mediated cartilage repair of OLTs., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This project was funded by a philanthropy gift from the Smead/Byram family. The position of I.K.S. at the Steadman Philippon Research Institute was partially supported by Arthrex. M.J.P has received consulting fees and royalties from Smith & Nephew; royalties and support for education from Linvatec Corporation; research support from Arthrex; speaking fees from Synthes GMBH; and hospitality payments from Siemens Medical Solutions USA. T.O.C. has received consulting fees and royalties from Arthrex and Stryker; holds stock in BICMD; and has received support for education from Gemini Mountain and Wright Medical. J.H. has received royalty payment from Cook Myosite. J.J.R. has received consulting fees from Smith & Nephew and a grant from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
- Published
- 2024
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