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

Arthritis Research & Therapy

Jiho Sohn¹  Ashley Lau²  Lixia Zhang²  Cameron L. Kirkwood²  Keith L. Kirkwood³  Sridhar Rachala⁴  Mary Bayers-Thering⁴  John M. Marzo⁴  Mark J. Anders⁴  Supinder Kour Bali⁵  Frank Beier⁵ 

[1] Department of Medicine, University at Buffalo, Buffalo, NY, USA;Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, 645 Biomedical Research Building, 3435 Main St, 14214-8006, Buffalo, NY, USA;Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, 645 Biomedical Research Building, 3435 Main St, 14214-8006, Buffalo, NY, USA;Department of Head and Neck/Plastic and Reconstructive Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA;Department of Orthopaedics, University at Buffalo, Buffalo, NY, USA;Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada;Western Bone and Joint Institute, University of Western Ontario, London, Ontario, Canada;

关键词: Osteoarthritis;    Myeloid-derived suppressor cells;    Osteoclasts;    Obesity;    Subchondral bone;   

DOI  :  10.1186/s13075-021-02663-z

来源: Springer

【 摘 要 】

BackgroundOsteoarthritis (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.MethodsIn 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.ResultsWe 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.ConclusionThese data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.

【 授权许可】

CC BY