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REVIEW: Mechanisms of TGFβ3 Action as a Therapeutic Agent for Promoting the Synthesis of Extracellular Matrix Proteins in Hyaline Cartilage

M. S. Bozhokin1,2,a*, Y. V. Sopova3,4,5, D. V. Kachkin4,5, A. A. Rubel4,5, and M. G. Khotin2

1Vreden Russian Scientific Research Institute of Traumatology and Orthopedics, 195427 St. Petersburg, Russia

2Institute of Cytology, Russian Academy of Science, 194064 St. Petersburg, Russia

3Vavilov Institute of General Genetics, Russian Academy of Science, St. Petersburg Branch, 199034 St. Petersburg, Russia

4St. Petersburg State University, Faculty of Biology, 199034 St. Petersburg, Russia

5St. Petersburg State University, Laboratory of Amyloid Biology, 199034 St. Petersburg, Russia

* To whom correspondence should be addressed.

Received January 4, 2020; Revised February 26, 2020; Accepted February 26, 2020
Hyaline cartilage is a nonvascular connective tissue covering the joint surface. It consists mostly of the extracellular matrix proteins and a small number of highly differentiated chondrocytes. At present, various techniques for repairing joint surfaces damage, for example, the use of modified cell cultures and biodegradable scaffolds, are under investigation. Molecular mechanisms of cartilage tissue proliferation have been also actively studied in recent years. TGFβ3, which plays a critical role in the proliferation of normal cartilage tissue, is one of the most important protein among cytokines and growth factors affecting chondrogenesis. By interacting directly with receptors on the cell membrane surface, TGFβ3 triggers a cascade of molecular interactions involving transcription factor Sox9. In this review, we describe the effects of TGFβ3 on the receptor complex activation and subsequent intracellular trafficking of Smad proteins and analyze the relation between these processes and upregulation of expression of major extracellular matrix genes, such as col2a1 and acan.
KEY WORDS: TGFβ3, mechanism of action, hyaline cartilage, Smad proteins, extracellular matrix

DOI: 10.1134/S0006297920040045