Therapeutics strategies
The Ongoing Challenge in osteoarthritis (OA) Treatment
Despite extensive research, a validated curative treatment for osteoarthritis (OA) remains elusive. Current options such as SYSADOAs (including glucosamine sulphate, curcumin, chondroitin sulphate) are controversial and have struggled to demonstrate a structural effect in humans. Similarly, selective biological approaches targeting inflammatory pathways, such as anti-TNFa and anti-IL-1b therapies, have shown limited or insignificant results. Senolytics (e.g. dasatinib, quercetin) also remain inconclusive in the treatment of OA. As a result, the focus of pharmacological treatment has been on symptom relief, typically with non-steroidal anti-inflammatory drugs, painkillers and sometimes intra-articular cortisone injections.
Our Breakthroughs in Glucocorticoid (GC) Research
Our research team has shed further light on the mechanisms by which glucocorticoids (GCs) work in the joint. Although commonly used in the treatment of OA, the precise effect of GC on fibrosis has not been fully understood. We have shown that prednisolone significantly reduces the expression of pro-fibrotic markers such as α-SMA and type III collagen, as well as cell proliferation and migration upon TGF-β stimulation. Importantly, our results showed that prednisolone in combination with the PPAR-ɣ agonist 15d-PGJ2 can attenuate pro-fibrotic pathways activated by TGF-β in human OA fibroblast-like synoviocytes1.
Exploring GC’s Effects on Cellular Senescence
In our recent studies, we have focused on the effects of GC on cellular senescence features in OA fibroblast-like synoviocytes. Our research has confirmed that GC do not exacerbate cellular senescence2. We did not observe an accumulation of β-galactosidase-positive cells, DNA damage or an increase in the expression of cyclin-dependent kinase inhibitors (CKIs) such as p21. In addition, prednisolone did not induce senescence in OA FLS, as evidenced by the unchanged proliferation rate, percentage of b-galactosidase-positive cells and CKI expression levels.
References
15-Deoxy-Δ-12, 14-prostaglandin J2 acts cooperatively with prednisolone to reduce TGF-β-induced pro-fibrotic pathways in human osteoarthritis fibroblasts
Vaamonde-Garcia C, Malaise O, Charlier E, Deroyer C, Neuville S, Gillet P, Kurth W, Meijide-Failde R, Malaise MG, de Seny D.
Biochem Pharmacol. 2019, 165:66-78
Malaise O, Paulissen G, Deroyer C, Ciregia F, Poulet C, Neuville S, Plener Z, Daniel C, Gillet P, Lechanteur C, Brondello JM, de Seny D, Malaise M.
J Clin Med. 2021, 10:5331.
