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. 2023 Apr 27;34(2):271-278.
doi: 10.52312/jdrs.2023.892.

Granzyme-A deficiency attenuates experimental osteoarthritis in mice, but perforin deficiency does not

Jorge Calvo, Llipsy Santiago, Maykel Arias, Julián Pardo, Jorge Albareda, Luis Martínez-Lostao, Felícito García-Alvarez  1
Affiliations

Granzyme-A deficiency attenuates experimental osteoarthritis in mice, but perforin deficiency does not

Jorge Calvo et al. Jt Dis Relat Surg. .

Abstract

Objectives: This study aims to assess the development of osteoarthritis (OA) in granzyme A- (gzmA) and B- (gzmB) and perforin- (perf) knockout mice.

Materials and methods: A total of 75 male and female C57BL/6 (eight to nine-week-old) mice were allocated to: gzmA-deficient (gzmA-/-) (11 females, 8 males), gzmB-deficient (gzmB-/-) (9 females, 8 males), perf-deficient (perf-/-) (10 females, 9 males), and control group (10 females, 10 males). Osteoarthritis was induced in the right knee by instability of the meniscus medial ligament. Sham surgery was practiced in the left knee. Knee samples obtained eight weeks after surgery were stained (Safranin-O) and blindly scored in lateral and medial femur and tibia using the Osteoarthritis Research Society International scale (OARSI) (from Grade 0, cartilage intact to 6, deformation), (five stages from 0, no OA to 4, >50% surface involvement); OARSI score (Grade x Stage); and a semi-quantitative scale from Grade 0 (normal) to 6 (cartilage erosion >80%).

Results: Significantly higher values in all scales in the right knees compared to the left knees in male and female mice were observed (p<0.05). Males of all strains showed in the right knee higher values than females on all scales. Deficiency of perforin did not modify OA severity in any sex. The gzmA-/- females presented less degenerative changes than the other groups.

Conclusion: Our study results show that sex plays an important role in the development of experimental OA in mice. Deficiency of gzmA can protect from the development of OA in female mice.

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Conflict of interest statement

Conflict of Interest: The authors have received economic help from Fondo Europeo de Desarrollo Regional, Gobierno de Aragón, Group B29_17R, Fundación Santander-Universidad de Zaragoza (Programa COVID-19), Agencia Estatal de Investigación 564 (PID2020-113963RBI00), Fundación Inocente, ASPANOA and Carrera de la Mujer de Monzón. LS is supported by a PhD fellowship (FPI) and by a postdoctoral fellowship 'Juan de la Cierva- Formación from the Ministry of Science, Innovation and Universities MA is supported by a postdoctoral fellowship 'Juan de la Cierva- incorporacion' from the Ministry of Science, Innovation and Universities. JP is supported by the ARAID Foundation.

Figures

Figure 1
Figure 1. Osteoarthritis (OA) severity according OARSI stage was compared in the right (OA model) and left knees in male and female groups. OARSI: Osteoarthritis Research Society International scale.
Figure 2
Figure 2. Glasson score values in control group in male (M) and female (F) in the different quadrants (femoral medial (FM), femoral lateral (FL), tibial medial (TM) and tibial lateral (TL).
Figure 3
Figure 3. OARSI stage in the right knees in wild type (C), gzmA-/-(A), gzmB-/-(group B) and perf-/-(P). OARSI: Osteoarthritis Research Society International scale.
Figure 4
Figure 4. Glasson score in gzmA, gzmB, and perf-deficient mice in male and female in the different quadrants. gzmA: Granzyme A; gzmB: Granzyme B; FM: Medial femoral condyle; FL: Lateral femoral condyle; TM: Medial tibial plateau; TL: Lateral tibial plateau.
Figure 5
Figure 5. Illustrates O-safranin staining carried out in both female and male mice of control, gzmA-/- and gzmB groups. Arrows indicate chondral damage. gzmA: Granzyme A; gzmB: Granzyme B.
See this image and copyright information in PMC

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