한빛사논문
- 조회1,150
Pranay Agarwal1,3, Hong-pyo Lee 2,3, Piera Smeriglio 1, Fiorella Grandi1, Stuart Goodman1, Ovijit Chaudhuri 2* and Nidhi Bhutani 1*
1Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, USA. 2Department of Mechanical Engineering, Stanford University, Stanford, CA, USA. 3These authors contributed equally: Pranay Agarwal, Hong-pyo Lee.
*Corresponding author
Abstract
Changes in the composition and viscoelasticity of the extracellular matrix in load-bearing cartilage influence the proliferation and phenotypes of chondrocytes, and are associated with osteoarthritis. However, the underlying molecular mechanism is unknown. Here we show that the viscoelasticity of alginate hydrogels regulates cellular volume in healthy human chondrocytes (with faster stress relaxation allowing cell expansion and slower stress relaxation restricting it) but not in osteoarthritic chondrocytes. Cellular volume regulation in healthy chondrocytes was associated with changes in anabolic gene expression, in the secretion of multiple pro-inflammatory cytokines, and in the modulation of intracellular calcium regulated by the ion-channel protein transient receptor potential cation channel subfamily V member 4 (TRPV4), which controls the phosphorylation of glycogen synthase kinase 3β (GSK3β), an enzyme with pleiotropic effects in osteoarthritis. A dysfunctional TRPV4–GSK3β pathway in osteoarthritic chondrocytes rendered the cells unable to respond to environmental changes in viscoelasticity. Our findings suggest strategies for restoring chondrocyte homeostasis in osteoarthritis.
논문정보
- Research article
- 2021년 03월 (BRIC 등록일 2021-03-22)
- 국외 연구진
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