Erdal Uzun1, Semih Güvercin1, Ali Eray Günay2, İbrahim Halil Kafadar1, Demet Bolat3, Arzu Hanım Yay3,4, Ahmet Güney1

1Department of Orthopedics and Traumatology, Medicine Faculty of Erciyes University, Kayseri, Türkiye
2Department of Orthopedics and Traumatology, Kayseri City Hospital, Kayseri, Türkiye
3Department of Histology and Embryology, Medicine Faculty of Erciyes University, Kayseri, Türkiye
4Erciyes University, Genome and Stem Cell Center, Kayseri, Türkiye

Keywords: Cartilage defect, hydroxychloroquine, oral, rabbit knee, treatment.


Objectives: This study aims to evaluate the time- and dose-dependent effects of oral hydroxychloroquine (HCQ) on focal full-thickness knee chondral defect healing in a rabbit model.

Materials and methods: Cartilage defects of 4x4 mm2 were created on both medial femoral condyles of 24 New Zealand rabbits. The rabbits were divided into six groups (A-F) according to HCQ administration and sacrifice time: A (three-week control) and B (six-week control) received no additional interventions; C (20 mg/kg HCQ, three weeks); D (20 mg/kg HCQ, six weeks); E (40 mg/kg HCQ, three weeks); and F (40 mg/kg HCQ, six weeks). Osteochondral specimens were evaluated macroscopically, histologically, and immunohistochemically. The terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method was used to detect apoptotic cells.

Results: The International Cartilage Repair Society (ICRS) scores were significantly higher in the experimental groups than in the controls (p<0.001). The Wakitani scores in Group D showed a significant improvement compared to those in Group B (p<0.01). The 20 mg/kg HCQ treatment groups showed better recovery than the controls (p<0.01). High-dose HCQ (40 mg/kg) treatment significantly reduced the intensity of collagen type 2 immunoreactivity compared to that in the groups receiving 20 mg/kg of HCQ (p<0.01). Collagen type 2 expression in Group F was significantly lower than that in Group D (p<0.01). There were more TUNEL-positive cells in the repair sites of Groups E and F than in the lower-dose experimental groups and untreated experimental groups (p<0.001).

Conclusion: A low dose of HCQ improved cartilage repair, while higher doses of HCQ exerted a negative effect on cartilage regeneration in rabbits. In the presence of defective cartilage, the use of HCQ at an appropriate dose and time is important for cartilage health.

Citation: Uzun E, Güvercin S, Günay AE, Kafadar İH, Bolat D, Hanım Yay A, et al. The effect of oral hydroxychloroquine on chondral defect: An experimental study. Jt Dis Relat Surg 2023;34(3):628- 639. doi: 10.52312/jdrs.2023.1114.

Ethics Committee Approval

The study protocol was approved by the Erciyes University Animal Experiments Local Ethics Committee (date: 02.12.2020, no: 20/164). The study was conducted in the facilities of the Orthopedics and Traumatology, Histology, and Experimental Animal Production and Research Center.

Author Contributions

Idea/concept: E.U., A.E.G., A.G.; Design: E.U., İ.H.K., D.B., A.H.Y.; Control/supervision: A.G., A.H.Y.; Data collection and/or processing: E.U., S.G., D.B.;Analysis and/or interpretation: E.U., İ.H.K., A.G.; Literature review: E.U., A.E.G., S.G., D.B.; Writing the article: E.U., A.H.Y., A.G.; Critical review: A.G., A.H.Y.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

TUBITAK 1002 program supported this study.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.