Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE]
Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y.
The Company of Biologists
Published 2018
The Company of Biologists
Published 2018
| Publication Date: |
2018-09-29
|
|---|---|
| Publisher: |
The Company of Biologists
|
| Print ISSN: |
0950-1991
|
| Electronic ISSN: |
1477-9129
|
| Topics: |
Biology
|
| Keywords: |
Musculoskeletal system
|
| Published by: |
| _version_ | 1836399059616661504 |
|---|---|
| autor | Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. |
| beschreibung | Yunyun Jin, Qian Cong, Jelena Gvozdenovic-Jeremic, Jiajie Hu, Yiqun Zhang, Robert Terkeltaub, and Yingzi Yang 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 Gα s in the Enpp1 –/– mice enhanced joint calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte hypertrophy by activating Gα s -PKA signaling. Our findings provide new insights into the mechanisms underlying Enpp1 regulation of joint integrity. |
| citation_standardnr | 6338791 |
| datenlieferant | ipn_articles |
| feed_id | 1748 |
| feed_publisher | The Company of Biologists |
| feed_publisher_url | http://www.biologists.com/ |
| insertion_date | 2018-09-29 |
| journaleissn | 1477-9129 |
| journalissn | 0950-1991 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | The Company of Biologists |
| quelle | Development |
| relation | http://dev.biologists.org/cgi/content/short/145/18/dev164830?rss=1 |
| schlagwort | Musculoskeletal system |
| search_space | articles |
| shingle_author_1 | Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. |
| shingle_author_2 | Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. |
| shingle_author_3 | Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. |
| shingle_author_4 | Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. |
| shingle_catch_all_1 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] Musculoskeletal system Yunyun Jin, Qian Cong, Jelena Gvozdenovic-Jeremic, Jiajie Hu, Yiqun Zhang, Robert Terkeltaub, and Yingzi Yang 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 Gα s in the Enpp1 –/– mice enhanced joint calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte hypertrophy by activating Gα s -PKA signaling. Our findings provide new insights into the mechanisms underlying Enpp1 regulation of joint integrity. Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. The Company of Biologists 0950-1991 09501991 1477-9129 14779129 |
| shingle_catch_all_2 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] Musculoskeletal system Yunyun Jin, Qian Cong, Jelena Gvozdenovic-Jeremic, Jiajie Hu, Yiqun Zhang, Robert Terkeltaub, and Yingzi Yang 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 Gα s in the Enpp1 –/– mice enhanced joint calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte hypertrophy by activating Gα s -PKA signaling. Our findings provide new insights into the mechanisms underlying Enpp1 regulation of joint integrity. Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. The Company of Biologists 0950-1991 09501991 1477-9129 14779129 |
| shingle_catch_all_3 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] Musculoskeletal system Yunyun Jin, Qian Cong, Jelena Gvozdenovic-Jeremic, Jiajie Hu, Yiqun Zhang, Robert Terkeltaub, and Yingzi Yang 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 Gα s in the Enpp1 –/– mice enhanced joint calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte hypertrophy by activating Gα s -PKA signaling. Our findings provide new insights into the mechanisms underlying Enpp1 regulation of joint integrity. Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. The Company of Biologists 0950-1991 09501991 1477-9129 14779129 |
| shingle_catch_all_4 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] Musculoskeletal system Yunyun Jin, Qian Cong, Jelena Gvozdenovic-Jeremic, Jiajie Hu, Yiqun Zhang, Robert Terkeltaub, and Yingzi Yang 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 Gα s in the Enpp1 –/– mice enhanced joint calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte hypertrophy by activating Gα s -PKA signaling. Our findings provide new insights into the mechanisms underlying Enpp1 regulation of joint integrity. Jin, Y., Cong, Q., Gvozdenovic-Jeremic, J., Hu, J., Zhang, Y., Terkeltaub, R., Yang, Y. The Company of Biologists 0950-1991 09501991 1477-9129 14779129 |
| shingle_title_1 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] |
| shingle_title_2 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] |
| shingle_title_3 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] |
| shingle_title_4 | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] |
| timestamp | 2025-06-30T23:36:57.638Z |
| titel | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] |
| titel_suche | Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling [RESEARCH ARTICLE] |
| topic | W |
| uid | ipn_articles_6338791 |