Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis.

ABSTRACT: Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear. Here, we investigated the pathogenic mechanisms driving melanoma-induced osteocyte death. Both in vivo models and in vitro assays were combined with untargeted RNA sequencing approaches to explore the pathways governing melanoma-induced osteocyte death. We could show that ferroptosis is the primary mechanism behind osteocyte death in the context of melanoma bone metastasis. HMOX1 was identified as a crucial regulatory factor in this process, directly involved in inducing ferroptosis and affecting osteocyte viability. We uncover a non-canonical pathway that inv

SUBMITTER: Jia Y 

PROVIDER: S-EPMC11735842 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature