English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of Food and Drug Administration ( FDA )‐approved drugs in  AXT  cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in  AXT  cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum ( ER ) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38  MAPK , and intracellular production of reactive oxygen species ( ROS ). Knockdown of  Atf4  or  Ddit3  restored cell viability after calcitriol treatment, indicating that the  ER  stress response was indeed responsible for the anti‐proliferative effect in  AXT  cells. Notably, the  ER  stress response was induced to a lesser extent in human osteosarcoma than in  AXT  cells, consistent with the weaker suppressive effect on cell growth in the human cells. Thus, the magnitude of  ER  stress induced by calcitriol might be an index of its anti‐osteosarcoma effect. Although mice treated with calcitriol exhibited weight loss and elevated serum calcium levels, a single dose was sufficient to decrease osteosarcoma tumor size  in vivo . Our findings suggest that calcitriol holds therapeutic potential for treatment of osteosarcoma, assuming that techniques to diminish its toxicity could be established. In addition, our results show that calcitriol could still be safely administered to osteosarcoma patients for its original purposes, including treatment of osteoporosis.

Calcitriol exerts an anti‐tumor effect in osteosarcoma by inducing the endoplasmic reticulum stress response