期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 179, 期 2, 页码 201-217出版社
WILEY
DOI: 10.1111/bph.15713
关键词
3D cell culture; bisphosphonates; bone remodelling; bone sarcoma; mechanobiology; mechanotransduction; osteosarcoma; pharmacology; therapy
Osteosarcoma, a common primary bone tumor, is influenced by mechanobiology in its pathogenesis. Mechanobiology-driven therapies can curb tumor progression by altering the physical microenvironment or inhibiting proteins associated with metastasis.
Osteosarcoma is one of the most common primary tumours of the bone, with a 5-year survival rate of less than 20% after the development of metastases. Osteosarcoma is highly predisposed in Paget's disease of the bone, and both have common characteristic skeletal features due to rapid bone remodelling. Osteosarcoma prognosis is location dependent, which further emphasizes the likely contribution of the bone microenvironment in its pathogenesis. Mechanobiology describes the processes involved when mechanical cues from the changing physical microenvironment of the bone are transduced to biological pathways through mechanosensitive cellular components. Mechanobiology-driven therapies have been used to curb tumour progression by direct alteration of the physical microenvironment or inhibition of metastasis-associated mechanosensitive proteins. This review emphasizes the contribution of mechanobiology to the progression of osteosarcoma and sheds light on current mechanobiology-based therapies and potential new targets for improving disease management. Additionally, the many different 3D models currently used to study osteosarcoma mechanobiology are summarized.
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