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Molecular basis of osteochondrodysplasias
Rossi lab

Antonio Rossi, PI


Tel: +39 0382 987229

       +39 0382 987228

Lab members

Chiara Gramegna Tota (senior post-doc)

Alessandra Leone (PhD student @Iuss/Unipv)

Asifa Khan (PhD student Horizon-MSCA)

Chiara Paganini (researcher @IRCCS S. Matteo Hospital, Pavia)


Cartilage is a connective tissue that, together with bone, forms the framework supporting the body as a whole.

The main functions of cartilage are:

i) to provide a framework on which bone deposition may begin through endochondral ossification and

ii) to cover joint surfaces, acting as a shock absorber and allowing bones to slide over one another. Chondrodysplasias are a huge family of genetic disorders caused by defects in genes involved in cartilage development and homeostasis.

These diseases have extensive heterogeneity, therefore they are extremely difficult to diagnose and treat. Our group is focused on disorders caused by defects in the biosynthesis of proteoglycans the main component of the cartilage extracellular matrix, together with collagen.

Our current research topics are:

1) biochemical characterization of new skeletal dysplasias caused by defects in proteoglycan biosynthesis;

2) deep phenotyping of validated animal models for Diastrophic dysplasia and Desbuquois dysplasia type 1;

3) development of potential therapeutic approaches to chondrodysplasias using animal models;

4) characterization of the osteoarthritic phenotype in animal models of skeletal disorders and comparison to common osteoarthritis.

Different methodological approaches are used including generation and characterization of murine models, cell cultures, expression studies at the RNA and protein level, histology, confocal microscopy, X-rays and microCT.

Our research will deliver new information on the molecular basis of cartilage disorders immediately leading to an increased chance to translate this knowledge into therapies for patients.

What we build and what we learn from rare diseases is extensible to common diseases, not only for the immediate goal of better diagnoses, but also for the long-term challenge of identifying drug targets for common diseases (i.e. osteoarthritis).


Identification of potential non-invasive biomarkers in diastrophic dysplasia. Paganini C, Carroll RS, Gramegna Tota C, Schelhaas AJ, Leone A, Duker AL, O'Connell DA, Coghlan RF, Johnstone B, Ferreira CR, Peressini S, Albertini R, Forlino A, Bonafé L, Campos-Xavier AB, Superti-Furga A, Zankl A, Rossi A, Bober MB. Bone. 2023;175:116838. doi: 10.1016/j.bone.2023.116838.

Biallelic variants in SLC35B2 cause a novel chondrodysplasia with hypomyelinating leukodystrophy. Guasto A, Dubail J, Aguilera-Albesa S, Paganini C, Vanhulle C, Haouari W, Gorría-Redondo N, Aznal-Sainz E, Boddaert N, Planas-Serra L, Schlüter A, Verdura E, Bruneel A, Rossi A, Huber C, Pujol A, Cormier-Daire V. Brain. 2022 Mar 24:awac110. doi: 10.1093/brain/awac110. Online ahead of print.

Improvement of the skeletal phenotype in a mouse model of diastrophic dysplasia after postnatal treatment with N-acetylcysteine. Paganini C, Gramegna Tota C, Monti L, Monti I, Maurizi A, Capulli M, Bourmaud M, Teti A, Cohen-Solal M, Villani S, Forlino A, Superti-Furga A, Rossi A. Biochem Pharmacol. 2021; 185:114452. doi: 10.1016/j.bcp.2021.114452.

Phenotypic Characterization of Immortalized Chondrocytes from a Desbuquois Dysplasia Type 1 Mouse Model: A Tool for Studying Defects in Glycosaminoglycan Biosynthesis. Gramegna Tota C, Valenti B, Forlino A, Rossi A, Paganini C. Int J Mol Sci. 2021; 22(17):9304. doi: 10.3390/ijms22179304.

Calcium activated nucleotidase 1 (CANT1) is critical for glycosaminoglycan biosynthesis in cartilage and endochondral ossification. Paganini C, Monti L, Costantini R, Besio R, Lecci S, Biggiogera M, Tian K, Schwartz JM, Huber C, Cormier-Daire V, Gibson BG, Pirog KA, Forlino A, Rossi A. Matrix Biol. 2019; 81:70-90. doi: 10.1016/j.matbio.2018.11.002.

Bone and connective tissue disorders caused by defects in glycosaminoglycan biosynthesis: a panoramic view. Paganini C, Costantini R, Superti-Furga A, Rossi A. FEBS J. 2019; 286(15):3008-3032. doi: 10.1111/febs.14984