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  • Single-cell mass cytometry reveals cross-talk between inflammation-dampening and inflammation-amplifying cells in osteoarthritic cartilage.

Single-cell mass cytometry reveals cross-talk between inflammation-dampening and inflammation-amplifying cells in osteoarthritic cartilage.

Science advances (2020-03-24)
Fiorella Carla Grandi, Reema Baskar, Piera Smeriglio, Shravani Murkherjee, Pier Francesco Indelli, Derek F Amanatullah, Stuart Goodman, Constance Chu, Sean Bendall, Nidhi Bhutani
ABSTRACT

Aging or injury leads to degradation of the cartilage matrix and the development of osteoarthritis (OA). Because of a paucity of single-cell studies of OA cartilage, little is known about the interpatient variability in its cellular composition and, more importantly, about the cell subpopulations that drive the disease. Here, we profiled healthy and OA cartilage samples using mass cytometry to establish a single-cell atlas, revealing distinct chondrocyte progenitor and inflammation-modulating subpopulations. These rare populations include an inflammation-amplifying (Inf-A) population, marked by interleukin-1 receptor 1 and tumor necrosis factor receptor II, whose inhibition decreased inflammation, and an inflammation-dampening (Inf-D) population, marked by CD24, which is resistant to inflammation. We devised a pharmacological strategy targeting Inf-A and Inf-D cells that significantly decreased inflammation in OA chondrocytes. Using our atlas, we stratified patients with OA in three groups that are distinguished by the relative proportions of inflammatory to regenerative cells, making it possible to devise precision therapeutic approaches.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
SB 431542 hydrate, ≥98% (HPLC), powder
Sigma-Aldrich
3-Isobutyl-1-methylxanthine, ≥99% (HPLC), powder
Sigma-Aldrich
BMS-345541, ≥98% (HPLC), powder