Lysosomal destabilization: A missing link between pathological calcification and osteoarthritis

Ye, Tao; Wang, Chenyu; Yan, Jianfei; Qin, Zixuan; Qin, Wenpin; Ma, Yuxuan; Wan, Qianqian; Lu, Weicheng; Zhang, Mian; Tay, Franklin R.; Jiao, Kai; Niu, Lina

doi:10.1016/j.bioactmat.2023.12.001

Cited by 5 publications

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Continuous‐Gradient Mineralized Hydrogel Synthesized via Gravitational Osmosis for Osteochondral Defect Repair

Sun,

Zhang,

et al. 2024

Adv Funct Materials

View full text Add to dashboard Cite

The repair of hierarchical osteochondral defects requires complex gradient reconstruction at different levels, with continuous‐gradient mineralization being crucial. Strategies for achieving continuous‐gradient mineralization have rarely been reported. Here, a continuous‐gradient mineralized hydrogel is prepared using simple gravitational osmosis of a ≈2 nm amorphous calcium phosphate nanocluster (ACPC) suspension into composite organic frameworks for osteochondral regeneration. During gravitational infiltration, ACPC underwent gradual mineralization, resulting in the spontaneous formation of hydroxyapatite (HAP). The continuous‐gradient mineralized hydrogel aligned closely with the normal osteochondral structure, thereby effectively promoting repair of the cartilage and subchondral bone. In the cartilage layer, organic compounds improved the oxidative stress environment induced by injury and complemented the extracellular matrix of the cartilage. In the subchondral bone layer, HAP from the continuously mineralized hydrogel induced intracellular calcium accumulation in mesenchymal stem cells (MSCs), activating calcium/calmodulin‐dependent protein kinase 2 (CaMK2) and promoting osteogenic differentiation of MSCs through the calcium signaling pathway. Ultimately, compared with the nongradient hydrogel, this innovative gradient mineralization method exhibited significantly enhanced regeneration capabilities for osteochondral defects, as evidenced by metrics, such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N). This holistic strategy provides hope in the field of osteochondral repair.

show abstract

Continuous‐Gradient Mineralized Hydrogel Synthesized via Gravitational Osmosis for Osteochondral Defect Repair

Sun,

Zhang,

et al. 2024

Adv Funct Materials

View full text Add to dashboard Cite

show abstract

Viscoelasticity of ECM and cells—origin, measurement and correlation

Liu,

Ling,

Liang

et al. 2024

Mechanobiology in Medicine

View full text Add to dashboard Cite

Genetic insights into serum cathepsins as diagnostic and therapeutic targets in knee and hip osteoarthritis

Shao,

Gao,

Han

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving the progressive degradation of the cartilage extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological and pathological processes, particularly in protein degradation. Excess cathepsins levels are reported to contribute to the development of OA. However, the causal relationship between the cathepsin family and knee and hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses to explore this causal association. Our results indicated that elevated serum levels of cathepsin O increase the overall risk of knee OA, while increased serum levels of cathepsin H enhance the risk of hip OA. Conversely, the reverse MR analyses did not reveal a reverse causal relationship between them. In summary, OA in different anatomical locations may genetically result from pathological elevations in different serum cathepsin isoforms, which could be utilized as diagnostic and therapeutic targets in clinical practice.

show abstract

Lysosomal destabilization: A missing link between pathological calcification and osteoarthritis

Cited by 5 publications

References 70 publications

Continuous‐Gradient Mineralized Hydrogel Synthesized via Gravitational Osmosis for Osteochondral Defect Repair

Continuous‐Gradient Mineralized Hydrogel Synthesized via Gravitational Osmosis for Osteochondral Defect Repair

Viscoelasticity of ECM and cells—origin, measurement and correlation

Genetic insights into serum cathepsins as diagnostic and therapeutic targets in knee and hip osteoarthritis

Contact Info

Product

Resources

About