REVIEW article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
ER-resident proteins are key players in cartilage and bone homeostasis
Provisionally accepted
- University Hospital Münster, Münster, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Hyaline cartilage is essential for bone formation and joint function. It contains a dense extracellular matrix that is produced in the ER of chondrocytes. Therefore, the ER contains a complex machinery of enzymes including chaperones, glycosyltransferases and hydroxylases that control folding, modification and secretion of newly synthesized matrix proteins. Loss or malfunction of ER-resident chaperones and proteins leads to misfolding and accumulation of matrix proteins in the ER. This causes ER stress and disrupts crucial cellular processes including chondrocyte differentiation, signaling and matrix production. During skeletal development, deficiency of ER chaperones disrupts cartilage and bone formation by impairing the folding and maturation of collagens and other matrix proteins, causing chondrodysplasia, pseudoachondroplasia and other skeletal diseases. Loss of ER-resident chaperones also impairs the integrity and stability of the cartilage matrix, promoting its degeneration during osteoarthritis. Due to the complexity of the ER protein processing machinery, the specific roles of ER-resident proteins in cartilage and bone homeostasis largely remain elusive. This review provides an overview of the most common ER-resident proteins and our current understanding of their function in cartilage homeostasis and disease.
Keywords: Cartilage, Extracellular Matrix, Endoplasmic Reticulum, Chaperone, Protein Folding, er stress
Received: 08 Jul 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Stücker, Rellmann, Schulte and Dreier. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sina Stücker, sina.stuecker@uni-muenster.de
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.