RT @lucasaganronald: CYCLING IS THE MOST BEAUTIFUL SPORT IN THE WORLD ❤️. 📷: andrea_pialo

RT @i_papantoniou: Our recent Advanced Science paper, explores the development of #magnetically augmented cartilaginous #organoids.This 4D….

RT @i_papantoniou: ⚡️Thrilled to announce that our @FWOVlaanderen project was funded! Looking fwd to further collaborate with the co-PIs @….

RT @DLanger6: Respiratory muscle dysfunction can be both a cause and consequence of respiratory failure. It is often reversible and should….

RT @TissueEngKulak: Always dreamed of a work-out of (your) muscles in a lab? This is your chance! We have a PhD vacancy on '4D bioprinting….

RT @FZaucke: I am more than excited that our manuscript (written by @ZsJeneiLanzl and myself) has been accepted for publication👇👇👇👇👇👇.Osteo….

RT @SilviaMonteag: Unlocking a Detrimental Role of IGF1 in Osteoarthritis: A New Target for Therapeutic Intervention? | Research Communitie….

Finally, a big shout-out and thank you to everyone who worked on this project: @AnaEscribano7 Frederique Cornelis @AstridRoover An Sermon @FredCailotto @SilviaMonteag. Thank you @FWO & @KULeuven for supporting this study! @DevReg_KULeuven @UZLeuven. 14/14.

We hope this research brings us one step closer to finding a disease-modifying therapy for osteoarthritis. Stay tuned as we explore new ways to target the Wnt-IGF1 axis in future therapeutic approaches. 13/14

Finally, decreasing IGF1 in articular chondrocytes from OA patients favors the restoration of a healthy molecular profile. By reducing IGF1, we can protect the joint from Wnt-driven damage while preserving cartilage integrity! 12/14

We then investigated the translational implications of the identified Wnt/IGF1 link using a clinically relevant mouse model of posttraumatic OA. Again, Igf1 deficient mice were protected against OA. 11/14

We also found TCF/LEF binding sites in the IGF1 gene promoter, highly conserved across species, indicating that IGF1 is a direct Wnt target gene! This provides a clear molecular mechanism for how Wnt signaling leads to increased IGF1 in the joint, driving OA. 10/14

To dive deeper in the molecular mechanisms underlying the Wnt-IGF1 link, we used luciferase reporter assays and chromatin immunoprecipitation (ChIP) experiments. Wnt signaling directly increases IGF1 as Wnt transcription factor TCF4 binds to the IGF1 gene promoter. 9/14

We also found that chondrocyte hypertrophy, where cartilage cells lose their healthy identity, was prevented in Igf1-deficient mice. This is critical because hypertrophic chondrocytes, positive for collagen type X, contribute to OA progression. 8/14

IGF1 is well-known for its role in growth and tissue repair, but its role in OA was difficult to define. We used mice with cartilage-specific Igf1 deletion. These mice developed less OA when Wnt signaling was hyper-activated, showing less cartilage damage! 7/14

We validated this in vivo, using 2 models of Wnt hyper-activation, DOT1L-inhibited mice and Frzb KO mice (lacking a Wnt antagonist). Both models exhibited increased IGF1 expression in their cartilage, supporting the Wnt-IGF1 connection. Why is this important for OA? 6/14

We began with human chondrocytes in which #DOT1L, a negative epigenetic regulator of Wnt, was inhibited, leading to hyper-activated Wnt signaling. Our bioinformatics analyses showed IGF1 as a prominent node in the transcriptional network—suggesting a Wnt-IGF1 link. 5/14

We used transcriptome datasets of articular cartilage with #Wnt hyper-activation to explore the molecular mechanisms at play. Our data revealed that #IGF1 is a key downstream effector of Wnt signaling in chondrocytes (cartilage cells). 4/14.

Our research highlights a potential avenue for therapy by focusing on #Wnt signaling, a key molecular pathway involved in joint health and disease. Hyper-activation of Wnt signaling is implicated in OA, but the downstream players driving Wnt joint damage remain elusive. 3/14.

Osteoarthritis (OA), the most common chronic joint disease, affects over 500M people globally. Progressive joint damage leads to pain & disability. No disease-modifying treatments exist for OA. As populations age & obesity rates rise, this public health challenge will grow. 2/14.