Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Positive Regulation of S-adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors

Loc Dinh Hoang
,
Eriko Aoyama
* ORCID logo ,
Miki Hiasa
,
Hiroshi Omote
,
Satoshi Kubota
,
Takuo Kuboki
ORCID logo ,
Masaharu Takigawa
* ORCID logo
Version 1 : Received: 5 November 2023 / Approved: 6 November 2023 / Online: 6 November 2023 (07:35:30 CET)

A peer-reviewed article of this Preprint also exists.

Hoang, L.D.; Aoyama, E.; Hiasa, M.; Omote, H.; Kubota, S.; Kuboki, T.; Takigawa, M. Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors. Int. J. Mol. Sci. 2023, 24, 17294. Hoang, L.D.; Aoyama, E.; Hiasa, M.; Omote, H.; Kubota, S.; Kuboki, T.; Takigawa, M. Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors. Int. J. Mol. Sci. 2023, 24, 17294.

Abstract

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate expression of differentiated phenotype of chondrocytes. We also found that cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2 and chondroitin sulfate biosynthetic enzymes. Blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

Keywords

S-adenosylmethionine; chondrocyte differentiation; CCN2; polyamine; ODC

Subject

Medicine and Pharmacology, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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