Dataset Information

Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling.

ABSTRACT: The differentiated phenotype of articular chondrocytes of synovial joints needs to be maintained throughout life. Disruption of the articular cartilage, frequently associated with chondrocyte hypertrophy and calcification, is a central feature in osteoarthritis (OA). However, the molecular mechanisms whereby phenotypes of articular chondrocytes are maintained and pathological calcification is inhibited remain poorly understood. Recently, the ecto-enzyme Enpp1, a suppressor of pathological calcification, was reported to be decreased in joint cartilage with OA in both human and mouse, and Enpp1 deficiency causes joint calcification. Here, we found that hedgehog (Hh) signaling activation contributes to ectopic joint calcification in the Enpp1-/- mice. In the Enpp1-/- joints, Hh signaling was upregulated. Further activation of Hh signaling by removing the patched 1 gene in the Enpp1-/- mice enhanced ectopic joint calcification, whereas removing Gli2 partially rescued the ectopic calcification phenotype. In addition, reduction of Gαs in the Enpp1-/- mice enhanced joint calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte hypertrophy by activating Gαs-PKA signaling. Our findings provide new insights into the mechanisms underlying Enpp1 regulation of joint integrity.

SUBMITTER: Jin Y

PROVIDER: S-EPMC6176935 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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<i>Enpp1</i> inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling.

Jin Yunyun Y Cong Qian Q Gvozdenovic-Jeremic Jelena J Hu Jiajie J Zhang Yiqun Y Terkeltaub Robert R Yang Yingzi Y

Development (Cambridge, England) 20180920 18

The differentiated phenotype of articular chondrocytes of synovial joints needs to be maintained throughout life. Disruption of the articular cartilage, frequently associated with chondrocyte hypertrophy and calcification, is a central feature in osteoarthritis (OA). However, the molecular mechanisms whereby phenotypes of articular chondrocytes are maintained and pathological calcification is inhibited remain poorly understood. Recently, the ecto-enzyme Enpp1, a suppressor of pathological calcif ...[more]

PMID: 30111653

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Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling.

Publications

<i>Enpp1</i> inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling.

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