Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip model

Nat Biomed Eng. 2019 Jul;3(7):545-557. doi: 10.1038/s41551-019-0406-3. Epub 2019 Jun 3.

Abstract

Owing to population aging, the social impact of osteoarthritis (OA)-the most common musculoskeletal disease-is expected to increase dramatically. Yet, therapy is still limited to palliative treatments or surgical intervention, and disease-modifying OA (DMOA) drugs are scarce, mainly because of the absence of relevant preclinical OA models. Therefore, in vitro models that can reliably predict the efficacy of DMOA drugs are needed. Here, we show, using a newly developed microphysiological cartilage-on-a-chip model that enables the application of strain-controlled compression to three-dimensional articular cartilage microtissue, that a 30% confined compression recapitulates the mechanical factors involved in OA pathogenesis and is sufficient to induce OA traits. Such hyperphysiological compression triggers a shift in cartilage homeostasis towards catabolism and inflammation, hypertrophy, and the acquisition of a gene expression profile akin to those seen in clinical osteoarthritic tissue. The cartilage on-a-chip model may enable the screening of DMOA candidates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / pharmacology
  • Antirheumatic Agents / pharmacology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Cell Culture Techniques
  • Cellular Microenvironment
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Collagen Type X / metabolism
  • Compressive Strength
  • Cytokines / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • In Vitro Techniques
  • Inflammation
  • Lab-On-A-Chip Devices*
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Middle Aged
  • Osteoarthritis / drug therapy
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Phenotype*
  • Stress, Mechanical
  • Transcriptome

Substances

  • Anti-Inflammatory Agents
  • Antirheumatic Agents
  • COL10A1 protein, human
  • COL2A1 protein, human
  • Collagen Type I
  • Collagen Type II
  • Collagen Type X
  • Cytokines
  • collagen type I, alpha 1 chain
  • MMP13 protein, human
  • Matrix Metalloproteinase 13