Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling

Authors

Lixia Zhang, University at Buffalo, The State University of New York
Cameron L. Kirkwood, University at Buffalo, The State University of New York
Jiho Sohn, Jacobs School of Medicine and Biomedical Sciences
Ashley Lau, University at Buffalo, The State University of New York
Mary Bayers-Thering, University at Buffalo, The State University of New York
Supinder Kour Bali, The University of Western Ontario
Sridhar Rachala, University at Buffalo, The State University of New York
John M. Marzo, University at Buffalo, The State University of New York
Mark J. Anders, University at Buffalo, The State University of New York
Frank Beier, The University of Western OntarioFollow
Keith L. Kirkwood, University at Buffalo, The State University of New York

Document Type

Article

Publication Date

12-1-2021

Journal

Arthritis Research and Therapy

Volume

23

Issue

1

URL with Digital Object Identifier

10.1186/s13075-021-02663-z

Abstract

Background: Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology. Methods: In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC quantitation in humans with OA pathology relative to obesity status. Results: We observed that MDSCs are expanded in mice and humans during obesity. MDSCs were expanded in peripheral blood of OA subjects relative to body mass index and in mice fed a high-fat diet (HFD) compared to mice fed a low-fat diet (LFD). In mice, monocytic MDSC (M-MDSC) was expanded in diet-induced obesity (DIO) with a further expansion after destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA (PTOA) (compared to sham-operated controls). M-MDSCs from DIO mice had a greater capacity to form osteoclasts in culture with increased subchondral bone osteoclast number. In humans, we observed an expansion of M-MDSCs in peripheral blood and synovial fluid of obese subjects compared to lean subjects with OA. Conclusion: These data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.

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