Site-1 protease is essential for endochondral bone formation in mice

Patra, Debabrata; Xing, Xiaoyun; Davies, Sherri; Bryan, Jennifer; Franz, Carl; Hunziker, Ernst B; Sandell, Linda J (2007). Site-1 protease is essential for endochondral bone formation in mice. Journal of cell biology, 179(4), pp. 687-700. New York, N.Y.: Rockefeller Institute Press 10.1083/jcb.200708092

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Site-1 protease (S1P) has an essential function in the conversion of latent, membrane-bound transcription factors to their free, active form. In mammals, abundant expression of S1P in chondrocytes suggests an involvement in chondrocyte function. To determine the requirement of S1P in cartilage and bone development, we have created cartilage-specific S1P knockout mice (S1P(cko)). S1P(cko) mice exhibit chondrodysplasia and a complete lack of endochondral ossification even though Runx2 expression, Indian hedgehog signaling, and osteoblastogenesis is intact. However, there is a substantial increase in chondrocyte apoptosis in the cartilage of S1P(cko) mice. Extraction of type II collagen is substantially lower from S1P(cko) cartilage. In S1P(cko) mice, the collagen network is disorganized and collagen becomes entrapped in chondrocytes. Ultrastructural analysis reveals that the endoplasmic reticulum (ER) in S1P(cko) chondrocytes is engorged and fragmented in a manner characteristic of severe ER stress. These data suggest that S1P activity is necessary for a specialized ER stress response required by chondrocytes for the genesis of normal cartilage and thus endochondral ossification.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie

UniBE Contributor:

Hunziker, Ernst Bruno

ISSN:

0021-9525

ISBN:

18025304

Publisher:

Rockefeller Institute Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:01

Last Modified:

06 Dec 2013 13:51

Publisher DOI:

10.1083/jcb.200708092

PubMed ID:

18025304

Web of Science ID:

000251077500014

URI:

https://boris.unibe.ch/id/eprint/26627 (FactScience: 75551)

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