Asset Details
Do you wish to reserve the book?
From Protein Misfolding to Extracellular Matrix Disorganisation: Understanding Disease Pathology in Rare Skeletal Dysplasias
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
From Protein Misfolding to Extracellular Matrix Disorganisation: Understanding Disease Pathology in Rare Skeletal Dysplasias
Do you wish to request the book?
From Protein Misfolding to Extracellular Matrix Disorganisation: Understanding Disease Pathology in Rare Skeletal Dysplasias
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
From Protein Misfolding to Extracellular Matrix Disorganisation: Understanding Disease Pathology in Rare Skeletal Dysplasias
2025
Overview
Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are rare, autosomal dominant skeletal dysplasias characterised by disproportionate short stature, joint deformities, and early-onset osteoarthritis. These conditions result from mutations in key cartilage extracellular matrix (ECM) components, including cartilage oligomeric matrix protein (COMP), matrilin-3, and type IX collagen. Although genetically and clinically heterogeneous, PSACH and MED share convergent pathogenic mechanisms. Misfolded mutant ECM proteins are retained within the endoplasmic reticulum (ER) of growth plate chondrocytes, triggering chronic ER stress and impairing chondrocyte proliferation, differentiation, and survival. Moreover, some of the mutant protein is secreted and incorporated into the matrix, leading to altered collagen fibrillogenesis, disrupted proteoglycan distribution, and compromised biomechanical integrity. These alterations extend beyond cartilage, impacting tendons, ligaments, and muscle–tendon junctions, contributing to joint laxity, impaired force transmission, and mild myopathy. This review discusses the structural and functional consequences of ECM disorganisation in PSACH and MED, highlighting its central role in disease progression and emphasising the importance of considering ECM abnormalities when developing therapeutic strategies for rare short stature-associated skeletal disorders.
Publisher
MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
Subject
/ Animals
/ Cartilage Oligomeric Matrix Protein - genetics
/ Cartilage Oligomeric Matrix Protein - metabolism
/ Collagen
/ Disease
/ Extracellular Matrix - metabolism
/ Extracellular Matrix - pathology
/ Extracellular Matrix Proteins - genetics
/ Extracellular Matrix Proteins - metabolism
/ Genes
/ Humans
/ Matrilin Proteins - genetics
/ Matrilin Proteins - metabolism
/ Mutation
/ Osteochondrodysplasias - genetics
/ Osteochondrodysplasias - metabolism
/ Osteochondrodysplasias - pathology
/ Proteins
/ Review
