Phenotypic Features of Articular Cartilage Cells in the Femoral Head in Congenital Hip Dislocation

Congenital hip dislocation is a manifestation of a severe degree of hip joint dysplasia, a disabling orthopedic pathology with unclear pathogenetic mechanisms and etiological factors. In congenital hip dislocation, dysplastic processes are identified in the cartilage tissue of the articular surface of the femoral head. Studying the phenotypic characteristics of the articular cartilage cells in the femoral head will help to understand the etiopathogenetic mechanisms of this pathology. The study aims to characterize the cell phenotypes in the femoral head articular cartilage associated with congenital hip dislocation. Material and methods. An immunohistochemical analysis was performed on a culture of articular hyaline cartilage cells from the femoral head obtained from 5 patients with congenital hip dislocation. Five cell culture passages were carried out. Statistical processing of the quantitative data was performed using Microsoft Excel software. Results. During culturing, two cell types of different phenotypes were obtained. Based on a positive immunocytochemical reaction with a key marker of chondrogenic differentiation (anti-type II collagen), the first cell type was identified as chondrocytes and chondroblasts. These are round and polygonal cells that form a monolayer. The second type consisted of process-bearing bipolar and multipolar cells, located in isolation, which exhibited a positive immunocytochemical reaction for the early neural markers PAX6, SOX1, SOX2, Musashi1, and the late neural marker NF200. These cells were defined as being of neural origin. Conclusion. The obtained data will help to assess the involvement of neural-origin cells in the etiopathogenetic mechanisms of congenital hip dislocation development. The interrelationship of the processes occurring during embryogenesis, such as altered migration of neural crest cells, their ectopic localization, and the development of hip joint dysplasia (congenital hip dislocation) requires further investigation.

1. Malakhov OA, Kralina SE. Vrozhdennyi vyvikh bedra (klinicheskaya kartina, diagnostika, konservativnoe lechenie). M. 2006. 128. (In Russ.).

2. Pakhomova NYu, Kozhevnikov VV, Strokova EL, Korytkin AA, Zhukov DV. Zaidman AM. Rol' molekulyarno-geneticheskogo metoda v sovremennykh aspektakh diagnostiki displazii tazobedrennogo sustava. Sovremennye problemy nauki i obrazovaniya. 2024;2:89. (In Russ.). doi: 10.17513/spno.33362.

3. Strokova EL, Pakhomova NYu, Shevchenko AI, Korytkin AA, Kozhevnikov VV, Zaidman AM. Fenotipicheskie osobennosti kletok rebernogo khryashcha pri voronkoobraznoi deformatsii grudnoi kletki. Sibirskij nauchnyj medicinskij zhurnal. 2023;43(6):203-209. (In Russ.). doi: 10.18699/SSMJ20230625.

4. Aki T, Hashimoto K, Ogasawara M, Itoi E. A whole-genome transcriptome analysis of articular chondrocytes in secondary osteoarthritis of the hip. PLoS One. 2018 Jun 26;13(6):e0199734. doi: 10.1371/journal.pone.0199734.

5. Bohaček I, Plečko M, Duvančić T, Smoljanović T, Vukasović Barišić A, Delimar D. Current knowledge on the genetic background of developmental dysplasia of the hip and the histomorphological status of the cartilage. Croat Med J. 2020 Jul 5;61(3):260-270. doi: 10.3325/cmj.2020.61.260.

6. Cho T, Tiffany-Castiglioni E. Neurofilament 200 as an indicator of differences between mipafox and paraoxon sensitivity in Sy5Y neuroblastoma cells. J Toxicol Environ Health A. 2004 Jul 9;67(13):987-1000. doi: 10.1080/15287390490447287.

7. Feldman G, Kappes D, Mookerjee-Basu J, Freeman T, Fertala A, Parvizi J. Novel mutation in Teneurin 3 found to co-segregate in all affecteds in a multi-generation family with developmental dysplasia of the hip. J Orthop Res. 2019 Jan 37(1):171-180. doi:10.1002/jor.24148.

8. Gil-Kulik P, Świstowska M, Krzyżanowski A, Petniak A, Kwaśniewska A, Płachno BJ, et al. Evaluation of the Impact of Pregnancy-Associated Factors on the Quality of Wharton's Jelly-Derived Stem Cells Using SOX2 Gene Expression as a Marker. Int J Mol Sci. 2022 Jul 10;23(14):7630. doi: 10.3390/ijms23147630.

9. Gkiatas I, Boptsi A, Tserga D, Gelalis I, Kosmas D, Pakos E. Developmental dysplasia of the hip: a systematic literature review of the genes related with its occurrence. EFORT Open. Rev. 2019 Oct 1;4(10):595-601. doi: 10.1302/2058-5241.4.190006.

10. Good P, Yoda A, Sakakibara S, Yamamoto A, Imai T, Sawa H, et al. The human Musashi homolog 1 (MSI1) gene encoding the homologue of Musashi/Nrp-1, a neural RNA-binding protein putatively expressed in CNS stem cells and neural progenitor cells. Genomics. 1998 Sep 15;52(3):382-4. doi: 10.1006/geno.1998.5456.

11. Hall B.K. The neural crest and neural crest cells in vertebrate development and evolution. Springer Science Business Media, LLC, 2010. 400.

12. Herger S, Vach W, Nüesch C, Liphardt AM, Egloff C, Mündermann A. Dose-response relationship of in vivo ambulatory load and mechanosensitive cartilage biomarkers-The role of age, tissue health and inflammation: A study protocol. PLoS One. 2022 Aug 19;17(8). doi: 10.1371/journal.pone.0272694.

13. Hernandez PA, Wells J, Usheva E, Nakonezny PA, Barati Z, Gonzalez R, Kassem L, Henson FMD. Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia. Sci Rep. 2020 Jan 17;10(1):627. doi: 10.1038/s41598-020-57431-x.

14. Karim A, Amin AK, Hall AC. The clustering and morphology of chondrocytes in normal and mildly degenerate human femoral head cartilage studied by confocal laser scanning microscopy. J Anat. 2018 Apr;232(4):686-698. doi: 10.1111/joa.12768.

15. Luo Y, Sinkeviciute D, He Y, Karsdal M, Henrotin Y, Mobasheri A, et al. The minor collagens in articular cartilage. Protein Cell. 2017 Aug 8(8):560-572. doi: 10.1007/s13238-017-0377-7.

16. Morys J, Borkowska P, Zielinska A, Kowalski J. Study of the influence of NGF-в gene overexpression in human mesenchymal stem cells on the expression level of SOX1 and neural pathway genes. Mol Biol Rep. 2022 Jun 49(6):4435-4441. doi: 10.1007/s11033-022-07283-7.

17. Osumi N, Shinohara H, Numayama-Tsuruta K, Maekawa M. Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem. Cells. 2008 Jul 26(7):1663-72. doi: 10.1634/stemcells.2007-0884.

18. Sela-Donenfeld D, Kalcheim C. Inhibition of noggin expression in the dorsal neural tube by somitogenesis: a mechanism for coordinating the timing of neural crest emigration. Development 2000 Nov 127(22):4845-54. doi: 10.1242/dev.127.22.4845.

19. Talmage MS, Nielson AN, Heflin JA, D'Astous JL, Fedorak GT. Prevalence of Hip Dysplasia and Associated Conditions in Children Treated for Idiopathic Early-onset Scoliosis-Don't Just Look at the Spine. J Pediatr Orthop. 2020 Jan;40(1):e49-e52. doi: 10.1097/BPO.0000000000001390.

20. Zaydman AM, Strokova EL, Pahomova NY, Gusev AF, Mikhaylovskiy MV, Shevchenko AI, et al. Etiopathogenesis of adolescent idiopathic scoliosis: review of the literature and new epigenetic hypothesis on altered neural crest cells migration in early embryogenesis as the key event. Med. Hypotheses. 2021 Jun 151:110585. doi: 10.1016/j.mehy.2021.11058.

21. Zaydman AM, Strokova EL, Kiseleva EV, Suldina LA, Strunov AA, Shevchenko AI, Laktionov PP, Subbotin VM. A New Look at Etiological Factors of Idiopathic Scoliosis: Neural Crest Cells. Int J Med Sci. 2018 Mar 6;15(5):436-446. doi: 10.7150/ijms.22894