Synovial Fluid Derived from Human Knee Osteoarthritis Increases the Viability of Human Adipose-Derived Stem Cells through Upregulation of FOSL1

Author:

Kitajima HironoriORCID,Sakamoto TakuyaORCID,Horie TetsuhiroORCID,Kuwano Ayane,Fuku AtsushiORCID,Taki Yasuhiko,Nakamura Yuka,Tanida Ikuhiro,Sunami Hiroshi,Hirata Hiroaki,Tachi Yoshiyuki,Yamamoto NaokiORCID,Iida Yasuo,Ishigaki YasuhitoORCID,Yamada SohsukeORCID,Shimodaira ShigetakaORCID,Shimizu YusukeORCID,Ichiseki Toru,Kaneuji Ayumi,Osawa Satoshi,Kawahara Norio

Abstract

Knee osteoarthritis (Knee OA) is an irreversible condition that causes bone deformity and degeneration of the articular cartilage that comprises the joints, resulting in chronic pain and movement disorders. The administration of cultured adipose-derived stem cells (ADSCs) into the knee joint cavity improves the clinical symptoms of Knee OA; however, the effect of synovial fluid (SF) filling the joint cavity on the injected ADSCs remains unclear. In this study, we investigated the effect of adding SF from Knee OA patients to cultured ADSCs prepared for therapeutic use in an environment that mimics the joint cavity. An increase in the viability of ADSCs was observed following the addition of SF. Gene expression profiling of SF-treated ADSCs using DNA microarrays revealed changes in several genes involved in cell survival. Of these genes, we focused on FOSL1, which is involved in the therapeutic effect of ADSCs and the survival and proliferation of cancer stem cells. We confirmed the upregulation of FOSL1 mRNA and protein expression using RT-PCR and western blot analysis, respectively. Next, we knocked down FOSL1 in ADSCs using siRNA and observed a decrease in cell viability, indicating the involvement of FOSL1 in the survival of ADSCs. Interestingly, in the knockdown cells, ADSC viability was also decreased by SF exposure. These results suggest that SF enhances cell viability by upregulating FOSL1 expression in ADSCs. For therapy using cultured ADSCs, the therapeutic effect of ADSCs may be further enhanced if an environment more conducive to the upregulation of FOSL1 expression in ADSCs can be established.

Funder

JSPS KAKENHI

Private University Research Branding Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan

Collaborative Research from Kanazawa Medical University

Shibuya Science Culture and Sports Foundation

Publisher

MDPI AG

Subject

General Medicine

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