Taurine alleviates endoplasmic reticulum stress in the chondrocytes from patients with osteoarthritis

Abstract

Osteoarthritis (OA), characterized by pain and stiffness, swelling, deformity and dysfunction of joints, affects large numbers of population. The purpose of this study was to discover the effects of taurine in human OA chondrocytes and explore the underlying mechanisms. 46 patients with different grades of OA were recruited. Of these patients, 24 underwent total knee replacement and cartilages were harvested. The mRNA expressions of type II collagen (Collagen II) and endoplasmic reticulum (ER) stress markers (GRP78, GADD153 and Caspase-12) in cartilages were quantified by qRT-PCR. Cell viability and apoptosis of patient-derived chondrocytes were assessed by the CCK-8 assay and flow cytometry assay, respectively. Meanwhile, protein levels of Collagen II and ER stress markers both in cartilages and chondrocytes were evaluated by Western blot. The mRNA and protein levels of Collagen II decreased as OA progressed, while the expressions of ER stress markers increased dramatically. HO induced ER stress in chondrocytes, as shown by the significant increase in the expression of ER stress markers, inhibited chondrocyte viability and Collagen II synthesis, promoted apoptosis. However, taurine treatment inhibited these above phenomena. These results indicated that taurine exhibited anti-OA effect by alleviating HO induced ER stress and subsequently inhibiting chondrocyte apoptosis.

Endoplasmic Reticulum Stress Is Involved in Baicalin Protection on Chondrocytes From Patients With Osteoarthritis

“…24 Taurine had cytoprotective effects on H 2 O 2 -stimulated chondrocytes via suppressing ER stress. 12 5,7,3 0 ,4 0 -tetramethoxyflavone had chondroprotective roles via blocking ER stress-mediated apoptosis. 25 Moreover, recent studies already proved the regulatory activities of baicalin on ER's function.…”

“…The culture of human OA chondrocytes was performed via a previously reported method. 12 We subdivided chondrocytes into 5 groups: control group, H 2 O 2 group (incubation with 0.5 mM H 2 O 2 for 4 hours at day 4), H 2 O 2 + baicalin group (pretreatment via 100 μM baicalin for 1 day before H 2 O 2 administration), H 2 O 2 + baicalin + Tm group (pretreatment with 2.5 μg/mL Tm and 100 μM baicalin for 1 day before H 2 O 2 treatment) and H 2 O 2 + baicalin + TUDCA group (pretreatment with 100 μM TUDCA and 100 μM baicalin for 1 day before H 2 O 2 treatment).…”

Molecular and Cellular Effects of Chemical Chaperone—TUDCA on ER-Stressed NHAC-kn Human Articular Chondrocytes Cultured in Normoxic and Hypoxic Conditions

“…Likewise, occurrence of ER stress has been demonstrated in chondrocytes of osteoarthritis cartilage in humans [ 12 , 13 ]. Increased levels of GRP78, PDI, CHOP, and caspase-12 have been detected in articular cartilage of OA patients, indicating the role of ER stress and ER stress-mediated apoptosis in OA progression [ 13 , 16 ]. Nevertheless, pathological events accompanying OA development are not the only ones causing ER stress in cartilage tissue.…”

“Lessons from Rare Forms of Osteoarthritis”

“…Pharmacological inhibition of ER stress responses by repurposing an antiepileptic drug carbamazine is being trialled as a therapy for metaphyseal chondrodysplasia type Schmid [ 69 ]. In vitro studies on chondrocytes have suggested markers such as peptides from Col II synthesis and ER stress markers (GRP78, CHOP/GADD153 and Caspase12) are reduced with the exposure to amino acids such as taurine or the flavonoid baicalin that target the H 2 O 2 induced pathway [ 70 , 71 ]. GRP 78 is the master regulator of the unfolded protein response.…”