SUMMARY. This study was aimed at investigating the effect of periodic and continuous administration of 1-34 fragment of parathyroid hormone (PTH) on the diffe-rentiation of bovine prechondroblasts maintained in chondrogenic and osteogenic media. In addition, the regeneration of cartilage tissue of outbred rats was studied in terms of the dependence of the mentioned process on the level of parathyroid hormone and the changes in subchondral bone. Monolayer cultures of bovine chondroprogenitor cells, maintained in osteogenic and chondrogenic media, were studied with periodic and continuous administration of 1-34 PTH with subsequent immunofluorescent analysis of relevant markers. Knee joints were also surgically operated to form the deficiency of arthrodial cartilage with further investigation of regeneration processes depending on the administration of PTH in vivo via histochemical analysis of surgically operated knee joints of rats. The data obtained testify to the modulating effect of PTH on chondrogenic differentiation of stem cells and therapeutic potential of this hormone for the restoration of cartilage tissue.
Keywords: parathyroid hormone, chondrocytes, stem cells, differentiation
Full text and supplemented materials
Free full text: PDFReferences
1. Compston, J.E., Skeletal actions of intermittent parathyroid hormone: Effects on bone remodeling and structure, Bone, 2007, vol. 40, no. 6, pp. 1447–1452. https://doi.org/10.1016/j.bone.2006.09.008
2. Jiang, Y., Zhao, J., Liao, E.Y., Dai, R.C., Wu, X.P., and Genant, H.K., Application of microCT assessment of 3D bone microstructure in preclinical and clinical studies, J. Bone Miner. Metab., 2005, vol. 23, pp. 122–131.
3. Kaback, L.A., Soung Do, Y., Naik, A., Geneau, G., Schwarz, E.M., Rosier, R.N., O’Keefe, R.J., and Drissi, H., Teriparatide (134 human PTH) regulation of osterix during fracture repair, J. Cell Biochem., 2008, vol. 105, pp. 219–226. https://doi.org/10.1002/jcb.21816
4. Chang, J.K., Chang, L.H., Hung, S.H., Wu, S.C., Lee, H.Y., Lin, Y.S., Chen, C.H., Fu, Y.C., Wang, G.J., and Ho, M.L., Parathyroid hormone 1–34 inhibits terminal differentiation of human articular chondrocytes and osteoarthritis progression in rats, Arthritis Rheum., 2009, vol. 60, pp. 3049–3060. https://doi.org/10.1002/art.24843
5. Harrington, E.K., Coon, D.J., Kern, M.F., and Svoboda, K.K., PTH stimulated growth and decreased Col-X deposition are phosphotidylinositol-3,4,5 triphosphate kinase and mitogen activating protein kinase dependent in avian sterna, Anat. Rec. (Hoboken), 2010, vol. 293, no. 2, pp. 225–234. https://doi.org/10.1002/ar.21072
6. Kudo, S., Mizuta, H., Takagi, K., and Hiraki, Y., Cartilaginous repair of full-thickness articular cartilage defects is induced by the intermittent activation of PTH/PTHrP signaling, Osteoarthritis Cartilage, 2011, vol. 19, no. 7, pp. 886–894. https://doi.org/10.1016/j.joca.2011.04.007
7. Mwale, F., Yao, G., Ouellet, J.A., Petit, A., and Antoniou, J., Effect of parathyroid hormone on type X and type II collagen expression in mesenchymal stem cells from osteoarthritic patients, Tissue Eng., 2010, vol. 16, no. 11, pp. 3449–3455. https://doi.org/10.1089/ten
8. Kao, R., Lu, W., Louie, A., and Nissenson, R., Cyclic AMP signaling in bone marrow stromal cells has reciprocal effects on the ability of mesenchymal stem cells to differentiate into mature osteoblasts versus mature adipocytes, Endocrine, 2012, vol. 42, no. 6, pp. 622–636. https://doi.org/10.1007/s12020-012-9717-9
9. Chen, B., Lin, T., Yang, X., Li, Y., Xie, D., and Cui, H., Intermittent parathyroid hormone (1–34) application regulates camp-response element binding protein activity to promote the proliferation and osteogenic differentiation of bone mesenchymal stromal cells, via the cAMP/PKA signaling pathway, Exp. Ther. Med., 2016, vol. 11, pp. 2399–2406. https://doi.org/10.3892/etm.2016.3177
10. Zhang, Y., Kumagai, K., and Saito, T., Effect of parathyroid hormone on early chondrogenic differentiation from mesenchymal stem cells, J. Orthop. Surg. Res., vol. 9, no. 68. doi https://doi.org/10.1186/s13018-014-0068-5