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Origin and function of cartilage stem/progenitor cells in osteoarthritis

Key Points

  • Human articular cartilage contains a population of stem or progenitor cells that can be isolated and characterized in vitro on the basis of having self-renewal, multilineage differentiation and migratory abilities

  • During human embryonic development, cartilage stem cells and cartilage progenitor cells represent distinct subpopulations; however, no single, specific cell marker can trace or distinguish these cell populations in vivo

  • Upon injury to healthy cartilage, cartilage stem/progenitor cells (CSPCs) emerge and migrate to the injury site where they are thought to participate in tissue reparative activities

  • CSPCs exhibit different phenotypes in the early and late stages of osteoarthritis (OA), specifically with respect to cell migratory ability

  • Changes in the distribution of CSPCs during OA progression suggest that these cells might be responsible for communication between the articular cartilage, subchondral bone and other joint tissues

  • CSPCs are a candidate therapeutic target for OA, potentially involving strategies to enhance joint resurfacing, extracellular matrix production or chondroprotection

Abstract

Articular cartilage is a physiologically non-self-renewing avascular tissue with a singular cell type, the chondrocyte, which functions as the load-bearing surface of the arthrodial joint. Injury to cartilage often progresses spatiotemporally from the articular surface to the subchondral bone, leading to development of degenerative joint diseases such as osteoarthritis (OA). Although lacking intrinsic reparative ability, articular cartilage has been shown to contain a population of stem cells or progenitor cells, similar to those found in many other adult tissues, that are thought to be involved in the maintenance of tissue homeostasis. These so-called cartilage-derived stem/progenitor cells (CSPCs) have been observed in human, equine and bovine articular cartilage, and have been identified, isolated and characterized on the basis of expression of stem-cell-related surface markers, clonogenicity and multilineage differentiation ability. However, the origin and functions of CSPCs are incompletely understood. We review here the current status of CSPC research and discuss the possible origin of these cells, what role they might have in cartilage repair, and their therapeutic potential in OA.

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Figure 1: Identification and stem-cell-like properties of CSPCs.
Figure 2: CSPC distribution in normal articular cartilage and during OA pathogenesis.
Figure 3: Schematic of degenerative disease progression in OA and possible CSPC-based therapies.

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Zixuan Zhao, Xinyi Chen, … Hanry Yu

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Acknowledgements

The authors acknowledge research support from the Commonwealth of Pennsylvania Department of Health (SAP 4100050913), the US Department of Defense (W81XWH-10-1-0850, W81XWH-08-2-0032 and W81XWH-13-2-0052) and the NIH (1U18TR000532), and editorial assistance from N. Baker.

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Correspondence to Rocky S. Tuan.

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Jiang, Y., Tuan, R. Origin and function of cartilage stem/progenitor cells in osteoarthritis. Nat Rev Rheumatol 11, 206–212 (2015). https://doi.org/10.1038/nrrheum.2014.200

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