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Delgado-Calle et al. Osteocytes promote bone destruction in multiple myeloma
Delgado-Calle et al. used a mouse model of multiple myeloma to investigate the role of osteocytes in bone destruction during the later stages of the disease.
When exposed to multiple myeloma cells in vivo, osteocytes from the mouse model showed a greater level of caspase-3-dependent apoptosis than osteocytes from control mice. The mouse model osteocytes also expressed high levels of sclerostin, which reduced Wnt signaling, so inhibiting differentiation of osteoblasts. Notch signaling and an increased in expression of Notch receptors, particularly those for Notch 2 and Notch 3, occurred as a direct result of direct contact between multiple myeloma cells and mice osteocytes. RANKL (TNFSF11) was also more highly expressed.
The authors concluded that apoptosis was initiated by Notch signaling activation. Once the apoptotic process began, RANKL expression by osteocytes increased further, the osteocytic Rankl/Opg (TNFRSF11B) ratio was amplified and osteocytic bone resorption was boosted locally.
Editor’s comment: This elegant study demonstrates that osteocyte-derived factors promote tumor cell proliferation and destruction in multiple myeloma. Previous findings reported that osteocytes also promote experimental prostate cancer bone metastasis but another study showed that osteocytes suppress breast cancer growth and bone metastasis. Given the central role of osteocytes in bone remodeling, the molecular mechanisms through which they contribute to bone metastasis needs to be more clearly understood.
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