Purpurin Alleviates Meniscal Senescence and Osteoarthritis by Blocking the Non‐Metabolic Function of Hexokinase 2
4 affiliations
- 1Department of Sports Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- 2Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- 3Department of Sports Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
- 4Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Abstract
Meniscal degeneration, characterised by extracellular matrix (ECM) loss and cellular senescence, plays a critical role in osteoarthritis (OA) progression, yet the underlying mechanisms remain unclear. Although hexokinase 2 (HK2) is recognised as a key glycolytic enzyme, its potential non-metabolic functions in the meniscus remain unexplored. In this study, HK2 expression was evaluated in human OA and normal meniscus tissues, and its non-metabolic effects were investigated in primary meniscal cells using overexpression, knockdown, and site-directed mutagenesis; protein interactions were analysed by immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP). HK2 was significantly upregulated in OA meniscal tissues, and overexpression of catalytically inactive HK2 promoted meniscal ECM degradation and cellular senescence in an MYH10-dependent manner. Mechanistically, HK2 enhanced the MYH10-PRKN interaction, inducing K48-linked ubiquitination of MYH10 at lysine 410 and its subsequent proteasomal degradation, thereby reducing COL1A1 mRNA stability. Purpurin, identified through virtual screening, disrupted the HK2-MYH10 interaction in vitro, prevented MYH10 degradation, and attenuated cellular senescence. In the destabilisation of the medial meniscus (DMM) mouse model, intra-articular injection of adeno-associated virus expressing catalytically inactive HK2 exacerbated OA progression, whereas purpurin treatment alleviated meniscal degeneration, ECM loss, and OA-associated pain. Collectively, HK2 promotes meniscal senescence and OA progression through a non-metabolic, MYH10-dependent mechanism, and purpurin represents a promising lead compound for disease-modifying osteoarthritis drug (DMOAD) development.
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BibTeX
@article{lin2026purpurin,
title = {{Purpurin Alleviates Meniscal Senescence and Osteoarthritis by Blocking the Non‐Metabolic Function of Hexokinase 2}},
author = {Zhencan Lin and Ming Li and Wei Li and Tianfa Xu and Zongrui Jiang and Yanlin Zhong and Aishan He and Xiaoyi Zhao and Dianbo Long and Yan Kang},
journal = {Cell proliferation},
year = {2026},
month = oct,
doi = {10.1111/cpr.70294},
url = {https://europepmc.org/article/PMC/PMC13719234},
note = {CC BY},
}
RIS
TY - JOUR
TI - Purpurin Alleviates Meniscal Senescence and Osteoarthritis by Blocking the Non‐Metabolic Function of Hexokinase 2
AU - Zhencan Lin
AU - Ming Li
AU - Wei Li
AU - Tianfa Xu
AU - Zongrui Jiang
AU - Yanlin Zhong
AU - Aishan He
AU - Xiaoyi Zhao
AU - Dianbo Long
AU - Yan Kang
PY - 2026
DA - 2026/10/29
JO - Cell proliferation
DO - 10.1111/cpr.70294
UR - https://europepmc.org/article/PMC/PMC13719234
AB - Meniscal degeneration, characterised by extracellular matrix (ECM) loss and cellular senescence, plays a critical role in osteoarthritis (OA) progression, yet the underlying mechanisms remain unclear. Although hexokinase 2 (HK2) is recognised as a key glycolytic enzyme, its potential non-metabolic functions in the meniscus remain unexplored. In this study, HK2 expression was evaluated in human OA and normal meniscus tissues, and its non-metabolic effects were investigated in primary meniscal cells using overexpression, knockdown, and site-directed mutagenesis; protein interactions were analysed by immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP). HK2 was significantly upregulated in OA meniscal tissues, and overexpression of catalytically inactive HK2 promoted meniscal ECM degradation and cellular senescence in an MYH10-dependent manner. Mechanistically, HK2 enhanced the MYH10-PRKN interaction, inducing K48-linked ubiquitination of MYH10 at lysine 410 and its subsequent proteasomal degradation, thereby reducing COL1A1 mRNA stability. Purpurin, identified through virtual screening, disrupted the HK2-MYH10 interaction in vitro, prevented MYH10 degradation, and attenuated cellular senescence. In the destabilisation of the medial meniscus (DMM) mouse model, intra-articular injection of adeno-associated virus expressing catalytically inactive HK2 exacerbated OA progression, whereas purpurin treatment alleviated meniscal degeneration, ECM loss, and OA-associated pain. Collectively, HK2 promotes meniscal senescence and OA progression through a non-metabolic, MYH10-dependent mechanism, and purpurin represents a promising lead compound for disease-modifying osteoarthritis drug (DMOAD) development.
SN - 0960-7722
SN - 1365-2184
ER -