NFATC1 (Nuclear Factor Of Activated T Cells 1)

In a murine model of MDA-MB-231-induced osteolytic lesions, oral administration of 10 mg/kg SHP099 reduces osteoclasts and prevents the trabecular bone loss. Our study identifies SHP2 as a druggable target for inhibiting breast cancer-induced osteoclast differentiation, positioning the specific inhibitors of SHP2 as potential drugs developed to treat tumour-induced osteolysis in the future.

NFATc3 was enriched at DREAM target promoters and associated with the DREAM complex, possibly via LIN9, a scaffolding protein of the Multi-Vulva class B (MuvB) core proteins. These findings reveal an unexpected role for NFATc3 in promoting DREAM target gene transactivation and suggest the calcium-NFATc3 axis as a molecular target in LUAD, enriched by DREAM complex activation.

Functional experiments demonstrate that both knockdown and overexpression of ASIC2 critically regulate glioma cell proliferation, invasion, and metastatic potential through mechanisms mediated by matrix metalloproteinase 2 (MMP2), calcineurin, and nuclear factor of activated T cells 1 (NFAT1) signaling pathways. These findings delineate a pivotal role for ASIC2 in governing glioma malignant behavior and establish its relevance as a potential molecular target for therapeutic intervention.

qPCR and flow cytometry analyses further confirmed that simvastatin exerted its therapeutic effects by suppressing the calcium signaling pathway and downregulating the expression of nuclear factor of activated T cells 3 (NFATC3). Collectively, our study demonstrates that simvastatin alleviates CD4+ T cell inflammatory responses in AIH through calcium-dependent signaling pathway.

Our findings demonstrate that γ-Mag inhibits osteoclastogenesis and bone resorption by targeting the PI3K/AKT/NF-κB pathway, thereby blunting the C-FOS/NFATc1 transcriptional program. This study establishes γ-Mag as a promising natural lead compound for the treatment of postmenopausal osteoporosis.

Mechanistically, these protective effects were mediated through inhibition of the TLR4/NF-κB signaling pathway. Overall, Zn glycine emerges as a promising nutritional strategy for preventing inflammation-driven bone loss via modulation of the gut-bone axis.

These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of RANK-mediated signaling pathways and prevention of bone loss in an animal model. However, further exploration of the potential of L-quebrachitol as an effective approach for osteoporosis is required.

Induction with hUCMSCs promotes both early and late osseointegration in osteoporotic animal models. These results highlight the efficacy of hUCMSCs in enhancing bone healing after implant placement under osteoporotic conditions.

These results suggest that local administration of MR16-1 may enhance CGRP expression, promote callus maturation, and accelerate fracture healing, indicating a potential role in bone repair.

In silico analyses supported these results showing binding affinity of BPZ with important key regulatory proteins. Collectively, the obtained data suggest that long-term exposure to BPZ results in cardiotoxicity mediated by oxidative stress, inflammation, apoptosis, and functional cardiac dysfunction.

Additionally, this review examines the interplay among molecular mechanisms that regulate osteoclast differentiation and activation under pathological and inflammatory conditions, elucidates their roles in osteoclast hyperactivation-related human diseases, and provides a comprehensive framework for understanding these processes. Finally, it underscores potential novel therapeutic strategies for osteoclast-related skeletal lytic diseases and highlights perspectives for future investigations.

In vivo, DMC administration rescued bone loss and restored bone strength in an ovariectomy (OVX) mouse model. In conclusion, this work establishes DMC as a potent immunomodulatory agent for treating osteoporosis and validates PTP1B as a new pharmacological target within the osteoimmune system.