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Connecting Joint Function to Chondrocyte Biology in Knee Osteoarthritis

Project description

Unravelling the mechanobiology of osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease that affects millions of people worldwide. The knees are most commonly affected by chronic pain, impaired mobility and significant disability. Despite ongoing research efforts, the precise mechanisms driving disease progression remain unclear and there is no definitive cure for OA. The ERC-funded OA-CONNECT aims to understand why the mechanical load that normally preserves cartilage integrity triggers degeneration in OA. Researchers will follow a multidisciplinary approach to unravel the association between joint mechanics and cell biology as well as identify the key drivers behind this interplay. This pioneering work aims to guide the design of effective therapies and enhance patient care quality.

Objective

Osteoarthritis (OA), a degenerative joint disease, debilitates the lives of 242 million people globally but remains without a cure.
The knee joint is most frequently affected, causing pain, loss of joint function, and reduced quality of life. OA-CONNECT
instigates an innovative approach to understanding the fundamental cause of OA by posing a question that could previously
never be answered: ‘What causes mechanical loads to switch from supporting to disrupting cartilage health in OA?’
OA-CONNECT introduces a unique, integrated approach CONNECT-ing joint function to chondrocyte biology to unravel
the OA Mechanome, the maladaptive dynamic interplay of mechanical and biological drivers of OA cartilage degeneration
across cellular-, tissue- and joint- scales by:
(1) Connecting the spatial mechanical and cell molecular dynamics underlying OA cartilage adaptation to loading, using multimodal
read-outs from spatial omics, functional microscopy, and high-field MRI.
(2) Predicting cartilage degeneration by connecting knee joint cartilage loads during movement to local cellular mechanobiological
processes, using a multi-scale mechanobiology-inspired adaptive modeling framework informed by datasets of (1).
(3) Elucidating cartilage degeneration probability and mechanotherapy success in subjects with early knee OA, integrating the
multi-scale model of (2) with machine learning, multi-variate and population-based methods leveraging the use of clinically
accessible ‘real-world’ data. Prospective cohort and proof-of-concept studies will capture the dynamics of mechanical and
biological drivers and the impact of three current mechanotherapies.
The field of OA needs a shift in focus as the approaches of the past 20 years could not bring the mechanistic insights required
to develop treatment strategies. By dissecting the Goldilocks problem of mechanical load, OA-CONNECT will initiate a
groundbreaking shift in unraveling mechanobiological drivers in an uncharted direction.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-ADG

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Host institution

KATHOLIEKE UNIVERSITEIT LEUVEN
Net EU contribution

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€ 3 283 437,00
Address
OUDE MARKT 13
3000 LEUVEN
Belgium

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Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
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Total cost

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