Development Of A Pro-Chondrogenic Therapy For Osteoarthritis Via Reprogramming Of Healing...

Universities and Institutes of France

France

May 30, 2022

Description

  • Organisation/Company: Université Clermont-Auvergne
  • Research Field: Biological sciences › Biology
  • Researcher Profile: First Stage Researcher (R1) Recognised Researcher (R2) Established Researcher (R3) Leading Researcher (R4)
  • Application Deadline: 30/05/2022 00:00 - Europe/Brussels
  • Location: France › Clermont-Ferrand
  • Type Of Contract: Temporary
  • Job Status: Full-time
  • Osteoarthritis (OA) is the most prevalent chronic joint disease, affecting 30–50% of adults over 65 years and is a very significant health problem in western countries The problem of OA has not been solved and its adverse impacts on individuals, populations and economies will continue to increase, more especially with an aging population. There are no approved drugs able to cure osteoarthritis, but only anti-inflammatory treatments, with the objectif to delay prosthetic surgery. Even if OA has been considered as a non inflammatory disease, involving mainly cartilage, is now well established that inflammation is highly involved in disease progression. This makes OA as a disease of the joint as the whole by involving cartilage, bone, and synovial membrane. Recent clinical studies highlightened that knee changes in OA were highly associated with activated macrophages as well as soluble marophages and cytokines markers in synovial fluid. Macrophages exhibit a high degree of plasticity and are classified as (1) activated (M1), with pro-inflammatory phenotypes and inducing TNF-, IL-6 et IL-1 cyytokines or (2) activated (M2) macrophages, with anti-inflammatory properties and producing immunoregulatory factors such as IL-10. It has been hypothetized that the imbalance of the M1/ M2 ratio in articular tissues could be highly related the disease stage, and that repolarization of M1 into M2 type macrophages could be a promising innovative approach for OA.

    This PhD offer takes place in an international research collaboration programm between UMR 1240 INSERM of Clermont Ferrand in France and Laval University of Quebec (Canada), with the objectives to evaluate an innovative strategy of targeting inflammation mediators for macrophage repolarization in OA models. The main objective of our research proposal is to establish the proof of concept that to targeting inflammatory mediators can induce the reprogramming of M1/M2 macrophages and to evaluate the structural and functional consequences at the joint level.

    To achieve this objective, the PhD student will have in charge, on cells line, as well on syniovial macrophages from human samples, the assessment of the repolarization efficacy of molecules synthetized in the two labs. The two best compounds will then be studied in vivo in osteoarthritic rodent models to assess their ability to reprogram M1/M2 macrophages, anti-inflammatory activity, structural and functional joint integrity. In addition, for each of the therapeutic approaches tested, a longitudinal follow-up of the in vivo models will be carried out using conventional preclinical imaging strategies such as CT scans, imaging targeting inflammation and hypoxia in nuclear medicine and fluorescence, but also imaging targeting proteoglycans by the radiotracer NTP 15-5 developed within our unit and currently in clinical transfer (NCT 04481230).

    Funding category: Contrat doctoral

    PHD title: Biology PhD

    PHD Country: France

    Offer Requirements Specific Requirements

    This project was firstly selected by Clermont University as « gradaute track NHM » (please refer to UCA website), and is now expected to succeed in the final selection after oral examination of the candidate (planned for 24th of june in Clermont Ferrand)

    Profile of the candidate

    The candidate must have a Master's degree following studies in biological sciences and must have high theoretical and practical skills in cell culture, animal physiology and experimental models. Skills in preclinical imaging, particularly radioisotope imaging, may be an additional asset. A motivated, rigorous, dynamic candidate with teamwork and written and oral communication skills is sought.

    Contact Information
  • Organisation/Company: Université Clermont-Auvergne
  • Organisation Type: Other
  • Website: https: // imost.uca.fr/english-version
  • Country: France