gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2022)

25. - 28.10.2022, Berlin

Epigenetic mechanotransduction between chondrocytes and osteoblasts via extracellular vesicles

Meeting Abstract

  • presenting/speaker Kai O. Böker - Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und plast. Chirurgie, Göttingen, Germany
  • Xiaobin Shang - Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und plast. Chirurgie, Göttingen, Germany
  • Shahed Taheri - Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und plast. Chirurgie, Göttingen, Germany
  • Wolfgang Lehmann - Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und plast. Chirurgie, Göttingen, Germany
  • Arndt F. Schilling - Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und plast. Chirurgie, Göttingen, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2022). Berlin, 25.-28.10.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocAB79-134

doi: 10.3205/22dkou634, urn:nbn:de:0183-22dkou6344

Veröffentlicht: 25. Oktober 2022

© 2022 Böker et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Osteoarthritis (OA) is described as an inflammation of bone that has spread to the joint. A close physical connection between subchondral bone and cartilage suggests biochemical and molecular interaction pathways at the bone-cartilage interface. In addition, extracellular vesicles (EVs) have been shown to mediate communication between different cell-types and can regulate recipient cells by transferring bioinformation (e.g. miRNAs). In the context of osteoarthritis (OA), miR-221-3p has been shown to have a mechanosensitive and paracrine function in cartilage. The question in this research project now addresses the possible role of EVs containing miR-221-3p for epigenetic communication of mechanical signals between chondrocytes and osteoblasts.

Methods: Chondrocytes (r-ACCs) and osteoblasts (r-OBs) were isolated and identified from newborn rats by enzymatic (Collagenase 2) digestion and plastic adherence. EVs of chondrocytes were isolated by an established ultrafiltration method. Nanoparticle tracking analysis was used to determine the size distribution and quantity of vesicles. In addition, EVs were identified by western blot of EV marker proteins. r-OBs were treated with various extracellular vesicles (+/- endogenous miR-221) and regulation of targets genes was analyzed by qPCR. Co-cultivations of r-ACCs and r-OBs were performed and the effect of miR-221 on r-OBs was investigated by alizarin red staining and gene expression analysis.

Results and conclusion: In silico analyses (Targetscan, miRWalk, miRDB) revealed putative targets of miRNA-221-3p (CDKN1B/p27, TIMP-3, Tcf7l2/TCF4, ARNT). Indeed, transfection of miRNA-221-3p into chondrocytes and osteoblasts lead to regulation of these targets. Coculture experiments of transfected chondrocytes with non-treated osteoblasts showed not only regulation of these target genes in osteoblasts but also inhibition of their bone formation capacity. Treatment of osteoblasts with chondrocyte-derived EVs confirmed these results. Overall, our study provides a new perspective on a putative communication pathway between chondrocytes and osteoblasts conveying a mechanically induced epigenetic signal through EVs. This could be important for processes at the bone-cartilage interface, such as OA development, physiological joint homeostasis, growth or fracture healing and cellular control of other tissue interfaces with different biomechanical properties.

Results were published in [1].


References

1.
Shang X, Böker KO, Taheri S, Lehmann W, Schilling AF. Extracellular Vesicles Allow Epigenetic Mechanotransduction between Chondrocytes and Osteoblasts. Int J Mol Sci. 2021 Dec 10;22(24):13282. DOI: 10.3390/ijms222413282 Externer Link