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OSTEOARTHRITIS

Censoring exosomal crosstalk in osteoarthritis

Nature Aging volume 1, pages 332–334 (2021)Cite this article

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Using mouse models of osteoarthritis (OA), a new study finds that osteoclasts secrete exosomes that deliver miRNAs to chondrocytes, leading to an increase in metalloproteinase activity in cartilage. A bone-specific inhibitor of exosome production can halt this process, hinting at a new therapeutic strategy for patients with OA.

Osteoarthritis (OA) is an age-related joint disease characterized by progressive heterogeneous changes in articular cartilage and subchondral bone (SCB). OA is the most common arthritic disease, with a population prevalence of over 20%. In total, 80% of these patients have limitations in movement, and 25% have serious restrictions in major daily activities of life. Currently, OA treatment is challenging, as there is no intervention that stops disease progression or restores lesioned cartilage, except for costly total joint replacement surgery at end-stage disease1. As a result, OA puts a high social and economic burden on society. In this issue of Nature Aging2, Liu and colleagues make a convincing case for the existence of a pathogenic exosomal microRNA (miRNA or miR) crosstalk between osteoclasts (bone-resorbing cells; OCs) and neighboring chondrocytes in OA. The authors show in a mouse model of OA and primary co-culture cell systems that a set of OC-associated miRNAs regulate gene expression in osteoblasts upon transfer via small extracellular vesicles called ‘exosomes’3. This unexpected cell-to-cell communication pathway was discovered a decade ago4 and has since been demonstrated to be relevant in health and disease. Exosomes control gene expression in a non-cell autonomous manner, and the authors show for the first time that exosomes’ production in OCs (OCs) can be targeted pharmacologically to delay OA progression in mice.

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Fig. 1: Mechanisms and potential clinical implications of exosomal crosstalk in OA.

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Authors and Affiliations

  1. Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

    Ingrid Meulenbelt & Yolande F. M. Ramos

  2. Department of Pathology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, the Netherlands

    S. Rubina Baglio & D. Michiel Pegtel

Authors
  1. Ingrid Meulenbelt
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  2. Yolande F. M. Ramos
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  3. S. Rubina Baglio
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  4. D. Michiel Pegtel
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Corresponding authors

Correspondence to Ingrid Meulenbelt or D. Michiel Pegtel.

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Competing interests

D.M.P. is the co-founder and chief scientist at exBiome BV, advisor of Takeda and receives research funding from Prediction Biosciences. All other authors declare no competing interests.

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Meulenbelt, I., Ramos, Y.F.M., Baglio, S.R. et al. Censoring exosomal crosstalk in osteoarthritis. Nat Aging 1, 332–334 (2021). https://doi.org/10.1038/s43587-021-00052-4

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