Table 3 Potential therapeutic agents for restoring organelle dysfunction in OA
From: Osteoarthritis: molecular pathogenesis and potential therapeutic options
Organelles | Therapeutic agents | Therapeutic target | Mechanism | Activity | Disadvantages | Ref. |
|---|---|---|---|---|---|---|
Mitochondria | Quercetin | Mitochondrial biogenesis | AMPK/SIRT1/PGC-1α pathway | Enhanced expression of AMPK, SIRT1, PGC-1α, NIRF1, NIRF2 and TFAM (murine meniscectomy model) | Unknown | |
Fibroblast growth factor 19 | Mitochondrial biogenesis | AMPK/SIRT1/PGC-1α pathway | Enhanced expression of AMPK PGC-1α and SIRT1 (murine chondrocytes) | Potential risk of metabolic disorders | ||
Omentin-1 | Mitochondrial biogenesis | PGC-1α/TFAM pathway | Enhanced expression of PGC-1α, NRF1 and TFAM | Unknown | ||
Catapol | Mitochondrial biogenesis | PGC-1α/TFAM pathway | Enhanced expression of PGC-1α, NRF1 and TFAM (murine ATDC5 chondrocytes) | Lack of in vivo studies | ||
Sestrin 2 | Mitochondrial biogenesis | AMPK/PGC-1α pathway | Enhanced expression of mtDNA copy number, PGC-1α, NIRF1, NIRF2 and TFAM (murine MIA-induced OA model) | Unknown | ||
Urolithin A | Mitophagy | PINK1/Parkin pathway | Upregulation of mitophagy-related proteins encoded genes and increased level of ph-Ub (human chondrocytes) | Limited repair ability of chondrocytes | ||
Dihydromyricetin | Mitophagy | PINK1/Parkin pathway | Activation of PINK1/Parkin-LC3B axis (murine chondrocytes) | Unknown | ||
Mitochonic acid-5 | Mitophagy | PINK1/Parkin pathway | ΔΨm Restoration, enhanced expression of LC3B, Parkin (Human OA chondrocytes) | Lack of in vivo studies | ||
α-ketoglutarate | Mitophagy | PINK1/Parkin pathway | Enhanced expression of PINK1, Parkin, TOMM7 (murine ACLT model) | Low oral bioavailability | ||
17b-estradiol | Mitophagy | SIRT1/AMPK/mTOR pathway | Enhanced expression of SIRT1, LC3 and TOM20 (murine ATDC5 chondrocytes) | Unknown | ||
Lysosome | Astaxanthin | Hydroxyapatite formation | Inhibited expression of RUNX2 | Inhibition of hypertrophic chondrocyte differentiation (murine TBHP-induced IVDD model) | Inconclusive effect in OA | |
Adseverin | Hydroxyapatite formation | Inhibited expression of RUNX2 and type X collagen | Inhibition of hypertrophic chondrocyte differentiation (murine meniscectomy model) | Unknown | ||
Melatonin | Hydroxyapatite formation | Inhibited expression of RUNX2 | Inhibition of chondrocyte mineralization (murine TBHP-induced chondrocytes) | Lack of in vivo studies | ||
CD11b agonists | Hydroxyapatite formation | May inhibit the expression of ALP and ANX V | May inhibit chondrocyte mineralization | Inconclusive results in OA | ||
KrĂĽppel-like factor 10 inhibitors | Hydroxyapatite formation | Inhibited gene expression of RUNX2 | Inhibition of chondrocyte mineralization (murine TBHP-induced chondrocytes) | No formulation available | ||
lymphoid enhancer-binding factor 1 (Lef1) inhibitors | Hydroxyapatite formation | Inhibited expression of RUNX2 | Inhibition of chondrocyte mineralization (murine Lef1 knock-out costal chondrocytes) | No formulation available | ||
Synovium-derived stromal cells | Hydroxyapatite formation | Inhibited expression of RUNX2 and type X collagen | Inhibition of hypertrophic chondrocyte differentiation (murine costal chondrocytes) | No formulation available | ||
ER | 4-PBA | ER stress | Assist protein folding | Inhibited expression of BiP, MMP-13, ADAMTS 5, and CHOP (murine meniscectomy model) | Unknown | |
TUDCA | ER stress | Assist protein folding | Inhibited expression of BiP and increased expression of type II collagen (human OA chondrocytes) | lack of in vivo studies | ||
MG-132 | ER stress | Assist protein folding | Alleviation of chondrocyte apoptosis and cartilage degradation (murine MIA-induced OA model) | Unknown | ||
HSP 70 | ER stress | Assist protein folding | Inhibition of expression of caspase 3 and restoring the biosynthesis of proteoglycan (murine MIA-induced OA model) | No adverse effects were reported | ||
HSP 90 A | ER stress | Assist protein folding | Alleviation of chondrocyte apoptosis (human OA chondrocytes) | No formulation available | ||
Salicin | ER stress | Inhibition of IRE1α phosphorylation by binding to the phosphorylation site of IRE1α | Inhibited expression of IRE1α-mediated apoptotic genes (IκBα, p65) (murine ACLT model) | No adverse effects were reported | ||
Vitexin | ER stress | Unknown | Inhibited expression of CHOP (murine TG-induced chondrocytes with ER stress) | Unknown | ||
Safranal | ER stress | Inhibition of PERK-ATF4-eIF2a signaling pathway via the activation of SIRT1 | Inhibited expression of CHOP (murine meniscectomy model) | Unknown | ||
Trehalose | ER stress | Unknown | Inhibited expression of BiP and CHOP (murine TBHP-induced chondrocytes) | lack of in vivo studies | ||
Dapagliflozin | ER stress | Inhibition of PERK-ATF4-eIF2a signaling pathway via the activation of SIRT1 | Inhibited expression of BiP, PERK, eIF2α, ATF4 and CHOP (murine IL-1β-induced chondrocytes) | Unknown |
