PT  - JOURNAL ARTICLE
AU  - A. Abou-Jaoude
AU  - M. Courtes
AU  - L. Badique
AU  - D. Elhaj Mahmoud
AU  - C. Abboud
AU  - M. Mlih
AU  - H. Justiniano
AU  - A. Lemle
AU  - S. Awan
AU  - J. Terrand
AU  - A. Niemeier
AU  - A. Barbero
AU  - X. Houard
AU  - P. Boucher
AU  - RL Matz
TI  - ShcA promotes chondrocyte hypertrophic commitment and osteoarthritis in mice through RunX2 nuclear translocation and YAP1 inactivation
AID  - 10.1101/2020.07.16.206870
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.16.206870
4099  - http://biorxiv.org/content/early/2020/07/17/2020.07.16.206870.short
4100  - http://biorxiv.org/content/early/2020/07/17/2020.07.16.206870.full
AB  - Chondrocyte hypertrophic differentiation, a key process in endochondral ossification (EO), is also a feature of osteoarthritis leading to articular cartilage destruction. ShcA (Src homology and Collagen A) is an adaptor protein that binds to the cytoplasmic tail of receptor tyrosine kinases. We found that deletion of ShcA in chondrocytes of mice inhibits hypertrophic differentiation, alters the EO process, and leads to dwarfism. ShcA promotes ERK1/2 activation, nuclear translocation of the master transcription factor for chondrocyte hypertrophy, RunX2, while maintaining the Runx2 inhibitor YAP1 in its cytosolic inactive form. This leads to hypertrophic commitment and expression of markers of hypertrophy, such as Collagen X. In addition, ShcA deletion in chondrocytes protects from age-related osteoarthritis development in mice. Our results reveal that ShcA integrates multiple stimuli which affect the intracellular signaling processes leading to the hypertrophic commitment of chondrocytes and osteoarthritis.Competing Interest StatementThe authors have declared no competing interest.