한빛사논문
- 조회410
Sunghyun Park1,2, Yoshie Arai1, Alvin Bello3, Hansoo Park3, Dohyun Kim1, Kyung-Soon Park2 and Soo-Hong Lee1,*
1Department Medical Biotechnology, Dongguk University Biomedi Campus, Goyang-si, Gyeonggi-do, Republic of Korea. 2Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea. 3School of Integrative Engineering, Chung-ang University, Seoul, Republic of Korea.
*Corresponding author.
Abstract
Osteoarthritis (OA) causes serious changes in the metabolic and signaling pathways of chondrocytes, including the mitogen-activated protein kinase (MAPK) pathway. However, the role of sprouty RTK signaling antagonist 4 (SPRY4), an inhibitor of MAPK, in the human cartilage tissues and chondrocytes remains to be understood. Here, using SPRY4 gene delivery into healthy and degenerated chondrocytes, we elucidated the role of SPRY4 in preventing chondrocyte hypertrophy. In addition to using the human cartilage tissues with the destabilization of the medial meniscus (DMM) model in Sprague-Dawley (SD) rats, the role of SPRY4 in cartilage tissues and chondrocytes was explored through their molecular and histological analyses. In order to determine the effects of SPRY4 on healthy human chondrocyte hypertrophy, small interfering RNA (siRNA) was used to knock down SPRY4. Lentiviral transduction of SPRY4 into degenerated human chondrocytes allowed us to investigate its ability to prevent hypertrophy. SPRY4 expression levels were higher in healthy human cartilage tissue and chondrocytes than in degenerated human cartilage tissues and hypertrophy-induced chondrocytes. The knockdown of SPRY4 in healthy chondrocytes caused an increase in hypertrophy, senescence, reactive oxygen species (ROS) production, and extracellular matrix (ECM) protease expression. However, all these factors decreased upon overexpression of SPRY4 in degenerated chondrocytes via regulation of the MAPK signaling pathway. We conclude that SPRY4 is a crucial indicator of osteoarthritis (OA) severity and could play an important role in preventing OA in the cartilage by inhibiting chondrocyte hypertrophy.
논문정보
- Research article
- 2021년 09월 (BRIC 등록일 2021-09-27)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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