Tauroursodeoxycholic acid (TUDCA) counters osteoarthritis by regulating intracellular cholesterol levels and membrane fluidity of degenerated chondrocytes

Arai, Yoshie; Choi, Bok Hee; Kim, Byoung Ju; Rim, Wongyu; Park, Sunghyun; Park, Hyoeun; Ahn, Jinsung; Lee, Soo−Hong

doi:10.1039/c9bm00426b

Cited by 31 publications

(32 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, apart from rescuing chondrocytes from ER stress and ER stress-induced apoptosis, TUDCA has been shown to augment cyclin D1 expression and cell proliferation; increase levels of chondrogenic markers such as SOX9, COL2, ACAN, and chondroitin sulfate; attenuate intracellular cholesterol; increase membrane fluidity; and enhance the expression of focal adhesion proteins such as vinculin, integrin α5, and integrin β1. Together, these findings suggest that TUDCA could be used as an alternative treatment for the restoration of cartilage damage in osteoarthritis [187,188].…”

Section: Therapeutic Perspectives and Limitationsmentioning

confidence: 78%

“…TUDCA/UDCA has been used in Chinese medicine for centuries, and hundreds of studies have already underscored its beneficial effects in the treatment of many pathological conditions. Nevertheless, TUDCA is constantly a very intriguing pharmacological agent and a growing number of pre-clinical and clinical research is still performed, unraveling novel aspects of TUDCA functioning [94,[182][183][184][185][186][187]. Although through the years this bile acid has been demonstrated to be a very efficient hepatoprotectant and ER stress alleviator, many innovative contemporary reports inform about its novel potential applications and molecular modes of action.…”

Section: Therapeutic Perspectives and Limitationsmentioning

confidence: 99%

“…Moreover, two recent reports have suggested beneficial effects of TUDCA in therapy of osteoarthritis [187,188]. Here, apart from rescuing chondrocytes from ER stress and ER stress-induced apoptosis, TUDCA has been shown to augment cyclin D1 expression and cell proliferation; increase levels of chondrogenic markers such as SOX9, COL2, ACAN, and chondroitin sulfate; attenuate intracellular cholesterol; increase membrane fluidity; and enhance the expression of focal adhesion proteins such as vinculin, integrin α5, and integrin β1.…”

Section: Therapeutic Perspectives and Limitationsmentioning

confidence: 99%

See 2 more Smart Citations

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Kusaczuk

2019

Cells

140

125

View full text Add to dashboard Cite

Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.

show abstract

Section: Therapeutic Perspectives and Limitationsmentioning

confidence: 78%

Section: Therapeutic Perspectives and Limitationsmentioning

confidence: 99%

Section: Therapeutic Perspectives and Limitationsmentioning

confidence: 99%

See 1 more Smart Citation

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Kusaczuk

2019

Cells

140

125

View full text Add to dashboard Cite

show abstract

“…Tauroursodeoxycholic acid (TUDCA), an endogenous chemical chaperone that protects cells against ER stress, has been shown to attenuate intestinal inflammation and barrier disruption in various disease models, such as DSS-induced colitis [173,174] and non-alcoholic fatty liver disease [175]. The effect of TUDCA in bone was also investigated in experimental models which displayed that TUDCA was comparable to recombinant human bone morphogenetic protein-2 possessing osteogenic potential in a mouse spinal injury model [176], and an alternative treatment to restore OA cartilage by balancing intracellular cholesterol levels in chondrocytes [177]. Therefore, targeting dysregulated UPR signaling in gut and/or bone marrow microenvironment may be proposed as new therapeutic strategy for IBD-associated bone destruction.…”

Section: Intestinal Barrier-regulated Bone Lossmentioning

confidence: 99%

Mechanisms Underlying Bone Loss Associated with Gut Inflammation

Arra

Abu‐Amer

2019

IJMS

View full text Add to dashboard Cite

Patients with gastrointestinal diseases frequently suffer from skeletal abnormality, characterized by reduced bone mineral density, increased fracture risk, and/or joint inflammation. This pathological process is characterized by altered immune cell activity and elevated inflammatory cytokines in the bone marrow microenvironment due to disrupted gut immune response. Gastrointestinal disease is recognized as an immune malfunction driven by multiple factors, including cytokines and signaling molecules. However, the mechanism by which intestinal inflammation magnified by gut-residing actors stimulates bone loss remains to be elucidated. In this article, we discuss the main risk factors potentially contributing to intestinal disease-associated bone loss, and summarize current animal models, illustrating gut-bone axis to bridge the gap between intestinal inflammation and skeletal disease.

show abstract

“…Although recent findings have demonstrated good efficiency of chemical chaperones in alleviating ER stress in broad spectrum of cell types, only a limited amount of data is available in terms of chemical chaperones function in chondrocytes [6,33]. Thus, in this study we investigated whether TUDCA was able to reduce ER stress, alleviate inflammation, restore collagen type II expression, and prevent apoptosis of human articular chondrocytes treated with IL-1β and tunicamycin (TNC).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

Osteoarthritis (OA) is considered one of the most common arthritic diseases characterized by progressive degradation and abnormal remodeling of articular cartilage. Potential therapeutics for OA aim at restoring proper chondrocyte functioning and inhibiting apoptosis. Previous studies have demonstrated that tauroursodeoxycholic acid (TUDCA) showed anti-inflammatory and anti-apoptotic activity in many models of various diseases, acting mainly via alleviation of endoplasmic reticulum (ER) stress. However, little is known about cytoprotective effects of TUDCA on chondrocyte cells. The present study was designed to evaluate potential effects of TUDCA on interleukin-1β (IL-1β) and tunicamycin (TNC)-stimulated NHAC-kn chondrocytes cultured in normoxic and hypoxic conditions. Our results showed that TUDCA alleviated ER stress in TNC-treated chondrocytes, as demonstrated by reduced CHOP expression; however, it was not effective enough to prevent apoptosis of NHAC-kn cells in either normoxia nor hypoxia. However, co-treatment with TUDCA alleviated inflammatory response induced by IL-1β, as shown by down regulation of Il-1β, Il-6, Il-8 and Cox2, and increased the expression of antioxidant enzyme Sod2. Additionally, TUDCA enhanced Col IIα expression in IL-1β- and TNC-stimulated cells, but only in normoxic conditions. Altogether, these results suggest that although TUDCA may display chondoprotective potential in ER-stressed cells, further analyses are still necessary to fully confirm its possible recommendation as potential candidate in OA therapy.

show abstract

Tauroursodeoxycholic acid (TUDCA) counters osteoarthritis by regulating intracellular cholesterol levels and membrane fluidity of degenerated chondrocytes

Abstract: TUDCA promote the chondrogenic properties of osteoarthritic chondrocytes at submicellar concentrations by reducing the intracellular cholesterol and increasing membrane fluidity.

Cited by 31 publications

References 48 publications

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Mechanisms Underlying Bone Loss Associated with Gut Inflammation

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

Contact Info

Product

Resources

About