Inflammatory and anti­inflammatory cytokine activity in the cartilage cells of genetically modified mice

Torgomyan A., Saroyan M.

Various genes level of activity in monolayer cultures of chondroprogenitor cells and chondrocytes isolated from articular cartilage of genetically modified mice was studied. Monolayer cultures of chondrocytes and chondroprogenitor cells were subjected to qPCR study to determine the target genes activity: col 2a1, Sox 9, Il 1a, Il 1b, CCL 2, CCL 3, CCL 4, CCL 5, MMP 3, MMP 13 and aggrecan (Aggr ). It was found that the activity of pro­inflammatory cytokines (Il1b, Il6, Il 8) is higher in chondroprogenitor cells, as well as the activity of metalloproteinases (MMP 3, MMP 13) responsible for the degradation of the matrix. Synthesis of type 2 collagen and agrecan in chondroprogenitor cells is higher than in chondrocytes, this pattern is observed in all strains of the studied animals. There is a high activity of type 2 collagen and aggrecan in both chondroprogenitor cells and chondrocytes of strain 6 isolated from the cartilage tissue, while the observed low activity of pro­inflammatory cytokines and metalloproteinases, which indicates a pronounced ability of this strain mice to repair damaged cartilage tissue.

Key words: cytokines, cartilage, mice, osteoarthritis

Tsitologiya i Genetika 2021, vol. 55, no. 4, pp. 77-78

• Yerevan State Medical University after M. Heratsi, Department of Physiology, Koryun 2, Yerevan, Armenia

E-mail: adelinatorgomyan yahoo.com

Torgomyan A., Saroyan M. Inflammatory and anti­inflammatory cytokine activity in the cartilage cells of genetically modified mice, Tsitol Genet., 2021, vol. 55, no. 4, pp. 77-78.

In "Cytology and Genetics":
A. Torgomyan & M. Saroyan Inflammatory and Anti-Inflammatory Cytokine Activity in the Cartilage Cells of Genetically Modified Mice, Cytol Genet., 2021, vol. 55, no. 4, pp. 396–403
DOI: 10.3103/S0095452721040125

References

1. Bedelbaeva, K., Snyder, A., Gourevitch, D., Clark, L., Zhang, X.M., Leferovich, J., et al., Lack of p21 expression links cell cycle control and appendage regeneration in mice, Proc. Natl. Acad. Sci. U. S. A., 2010, vol. 107, p. 5845e50. https://doi.org/10.1073/pnas.1000830107

2. Blankenhorn, E.P., Bryan, G., Kossenkov, A.V., Clark, L.D., Zhang, X.M., and Chang, C., Genetic loci that regulate healing and regeneration in LG/J and SM/J mice, Mamm. Genome, 2009, vol. 20, p. 720e33. https://doi.org/10.1007/s00335-009-9216-3

3. Blasioli, D.J., Kaplan, D.L., The roles of catabolic factors in the development of osteoarthritis, Tissue Eng. Part B Rev., 2014, vol. 20, no. 4, pp. 355–363. https://doi.org/10.1089/ten.teb.2013.0377

4. Brophy, R.H., Rai, M.F., Zhang, Z., Torgomyan, A., and Sandell, L.J., Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear, J. Bone Joint Surg. Am., 2012, vol. 94, no. 5, pp. 385–393. https://doi.org/10.2106/JBJS.K.00919

5. Deshpande, B.R., Katz, J.N., Solomon, D.H., Yelin, E.H., Hunter, D.J., Messier, S.P., Suter, L.G., and Losina, E., Number of persons with symptomatic knee osteoarthritis in the US: impact of race and ethnicity, age, sex, and obesity, Arthritis Care Res. (Hoboken), 2016, vol. 68, p. 1743e50. https://doi.org/10.1002/acr.22897

6. Ding, C., Cicuttini, F., and Jones, G., How important is MRI for detecting early osteoarthritis?, Nat. Clin. Pract. Rheumatol., 2008, vol. 4, no. 1, pp. 4–5. https://doi.org/10.1038/ncprheum0676

7. Dowthwaite, G.P., Bishop, J.C., Redman, S.N., Khan, I.M., Rooney, P., et al., The surface of articular cartilage contains a progenitor cell population, J. Cell Sci., 2004, vol. 117, pp. 889–897. https://doi.org/10.1242/jcs.00912

8. Eltawil, N.M., De Bari, C., Achan, P., Pitzalis, C., and Dell’accio, F., A novel in vivo murine model of cartilage regeneration. Age and strain-dependent outcome after joint surface injury, Osteoarthritis Cartilage, 2009, vol. 17, no. 6, pp. 695–704. https://doi.org/10.1016/j.joca.2008.11.003

9. Fitzgerald, J., Rich, C., Burkhardt, D., Allen, J., Herzka, A.S., and Little, C.B., Evidence for articular cartilage regeneration in MRL/MpJ mice, Osteoarthritis Cartilage, 2008, vol. 16, p. 1319e26. https://doi.org/10.1016/j.joca.2008.03.014

10. Goldring, M., Tsuchimochi, K., Ijiri, K., The control of chondrogenesis, J. Cell Biochem., 2006, vol. 97, pp. 33–44. https://doi.org/10.1002/jcb.20652

11. Hunter, D.J., Snieder, H., March, L., and Sambrook, P.N., Genetic contribution to cartilage volume in women: a classical twin study, Rheumatology (Oxford), 2003, vol. 42, p. 1495e500. https://doi.org/10.1093/rheumatology/keg400

12. Lories, R.J. and Monteagudo, S., Review article: is Wnt signaling an attractive target for the treatment of osteoarthritis?, Rheumatol. Ther., 2020, vol. 7, no. 2, pp. 259–270. https://doi.org/10.1007/s40744-020-00205-8

13. Mihanfar, A., Shakouri, S.K., Khadem-Ansari, M.H., Fattahi, A., Latifi, Z., Nejabati, H.R., and Nouri, M., Exosomal miRNAs in osteoarthritis, Mol. Biol. Rep., 2020, vol. 47, no. 6, pp. 4737–4748. https://doi.org/10.1007/s11033-020-05443-1

14. Nelson, A.E., Osteoarthritis year in review 2017: clinical osteoarthritis and cartilage, 2018, vol. 26, p. 319e325.https://doi.org/10.1016/j.joca.2017.11.014

15. Rai, M.F., Hashimoto, S., Johnson, E.E., Janiszak, K.L., Fitzgerald, J., Heber-Katz, E., et al., Heritability of articular cartilage regeneration and its association with ear-wound healing, Arthritis Rheumatol., 2012, vol. 64, no. 7, pp. 2300–2310. https://doi.org/10.1002/art.34396

16. Rice, S.J., Beier, F., Young, D., and Loughlin, J., Interplay between genetics and epigenetics in osteoarthritis, Nat. Rev. Rheumatol., 2020, vol. 16, no. 5, pp. 268–281. https://doi.org/10.1038/s41584-020-0407-3

17. Torgomyan, A. and Saroyan, M., Molecular mechanisms of chondro- and osteogenesis disturbance in osteoarthritis and ways of their correction, Cytol. Genet., 2020, vol. 54, no. 4, pp. 347–352. ISSN 0095-4527. https://doi.org/10.3103/s0095452720040118

18. Vasilceac, F.A., Marqueti, R.C., Neto, I.V.S., Nascimento, D.C., Souza, M.C., Durian, J.L.Q., and Mattiello, S.M., Resistance training decreases matrix metalloproteinase-2 activity in quadriceps tendon in a rat model of osteoarthritis, Braz. J. Phys. Ther., 2020, S1413-3555(19)30309-0. https://doi.org/10.1016/j.bjpt.2020.03.002