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Dernière publication 19/08/2025

Neutralization of acyl CoA binding protein -ACBP- for the experimental treatment

The plasma concentrations of acyl CoA binding protein (ACBP) encoded by the gene diazepam binding inhibitor (DBI) are increased in patients with...

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    [title] => Neutralization of acyl CoA binding protein -ACBP- for the experimental treatment
    [paragraph] => Neutralization of acyl CoA binding protein -ACBP- for the experimental treatment of osteoarthritis
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Authors
Nogueira-Recalde, Uxía, Lambertucci, Flavia, Montégut, Léa, Motiño, Omar, Chen, Hui, Lachkar, Sylvie, Anagnostopoulos, Gerasimos, Stoll, Gautier, Li, Sijing, Carbonier, Vincent, Saavedra Díaz, Ester, Blanco, Francisco J., van Tetering, Geert, de Boer, Mark, Maiuri, Maria Chiara, Caramés, Beatriz, Martins, Isabelle, Kroemer, Guido

 Lab

Journal
Cell Death & Differentiation
Abstract
The plasma concentrations of acyl CoA binding protein (ACBP) encoded by the gene diazepam binding inhibitor (DBI) are increased in patients with severe osteoarthritis (OA). Here, we show that knee OA induces a surge in plasma ACBP/DBI in mice subjected to surgical destabilization of one hind limb. Knockout of the Dbi gene or intraperitoneal (i.p.) injection of a monoclonal antibody (mAb) neutralizing ACBP/DBI attenuates OA progression in this model, supporting a pathogenic role for ACBP/DBI in OA. Furthermore, anti-ACBP/DBI mAb was also effective against OA after its intraarticular (i.a.) injection, as monitored by sonography, revealing the capacity of ACBP/DBI to locally reduce knee inflammation over time. In addition, i.a. anti-ACBP/DBI mAb improved functional outcomes, as indicated by the reduced weight imbalance caused by OA. At the anatomopathological level, i.a. anti-ACBP/DBI mAb mitigated histological signs of joint destruction and synovial inflammation. Of note, i.a. anti-ACBP/DBI mAb blunted the OA-induced surge of plasma ACBP/DBI, as well as that of other inflammatory factors including interleukin-1α, interleukin-33, and tumor necrosis factor. These findings are potentially translatable to OA patients because joints from OA patients express both ACBP/DBI and its receptor GABAARγ2. Moreover, a novel mAb against ACBP/DBI recognizing an epitope conserved between human and mouse ACBP/DBI demonstrated similar efficacy in mitigating OA as an anti-mouse ACBP/DBI-only mAb. In conclusion, ACBP/DBI might constitute a promising therapeutic target for the treatment of OA.
Keywords/Topics
 osteoarthritis
BIOSEB Instruments Used:
Static Weight Bearing Touch: Incapacitance Test (BIO-SWB-TOUCH-M)
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Test non douloureux pour mesurer le niveau d'inconfort (incapacitance) de petits animaux comme les rats et les souris via leur équilibre postural - indépendamment de l'opérateur. Le test de distribution pondérale statique est l'instrument idéal pour vos recherches en nociception et analgésie impliquant des rongeurs: arthrose, dégénération du cartilage, modèles d'inflammation, modèles de traumatismes nerveux , et bien plus... Notre nouveau SWB-Touch inclue désormais un tout nouvel écran tactile!

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