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Mechanisms of synovial joint and articular cartilage development

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Abstract

Articular cartilage is formed at the end of epiphyses in the synovial joint cavity and permanently contributes to the smooth movement of synovial joints. Most skeletal elements develop from transient cartilage by a biological process known as endochondral ossification. Accumulating evidence indicates that articular and growth plate cartilage are derived from different cell sources and that different molecules and signaling pathways regulate these two kinds of cartilage. As the first sign of joint development, the interzone emerges at the presumptive joint site within a pre-cartilage tissue. After that, joint cavitation occurs in the center of the interzone, and the cells in the interzone and its surroundings gradually form articular cartilage and the synovial joint. During joint development, the interzone cells continuously migrate out to the epiphyseal cartilage and the surrounding cells influx into the joint region. These complicated phenomena are regulated by various molecules and signaling pathways, including GDF5, Wnt, IHH, PTHrP, BMP, TGF-β, and FGF. Here, we summarize current literature and discuss the molecular mechanisms underlying joint formation and articular development.

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Abbreviations

BMP:

Bone morphogenic protein

CDMP1:

Cartilage-derived morphogenetic protein 1

cKO:

Conditional knockout

FGF:

Fibroblast growth factor

FGFR3:

Fibroblast growth factor receptor 3

GAG:

Glycosaminoglycan

GDF5:

Growth differentiation factor 5

IHH:

Indian hedgehog

MAPK:

Mitogen-activated protein kinase

NICD:

Notch intracellular domain

PTHrP:

Parathyroid hormone-related protein

Prg4:

Progeoglycan 4

SFZ:

Superficial zone

TGF-β:

Transforming growth factor-β

Tgfbr2:

TGF-β type II receptor

UDPGD:

Uridine diphosphoglucose dehydrogenase

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  1. Bone and Cartilage Regenerative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Ryota Chijimatsu

  2. Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Taku Saito

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Chijimatsu, R., Saito, T. Mechanisms of synovial joint and articular cartilage development. Cell. Mol. Life Sci. 76, 3939–3952 (2019). https://doi.org/10.1007/s00018-019-03191-5

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  • DOI: https://doi.org/10.1007/s00018-019-03191-5

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