NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma.

Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS.

Positive-Feedback Regulation of Subchondral H-Type Vessel Formation by Chondrocyte Promotes Osteoarthritis Development in Mice.

Vascular-invasion-mediated interactions between activated articular chondrocytes and subchondral bone are essential for osteoarthritis (OA) development. Here, we determined the role of nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) signaling in the crosstalk across the bone cartilage interface and its regulatory mechanisms. Then mice with chondrocyte-specific mTORC1 activation (Tsc1 CKO and Tsc1 CKO ) or inhibition (Raptor CKO ) and their littermate controls were subjected to OA induced by destabilization of the medial meniscus (DMM) or not.

Isoimperatorin ameliorates osteoarthritis by downregulating the mammalian target of rapamycin C1 signaling pathway.

Osteoarthritis (OA) is the most common disease of the joints, and is characterized by the breakdown of cartilage and degradation of the extracellular matrix. OA causes a high level of patient suffering and incurs large societal costs; however, the current strategies for treating OA are restricted due to limited understanding of the underlying molecular and cellular mechanisms. In the present study, the beneficial effects of isoimperatorin (Iso) were investigated using an experimental mouse model of OA, and its mechanism of action on primary chondrocytes was elucidated.