Fig. 7: CXCL7 activates the JAK/STAT3 pathway, resulting in the upregulation of MMP13 and C-myc, further promoting osteoclast signaling pathway activation and tumor proliferation. | Cell Death & Disease

Fig. 7: CXCL7 activates the JAK/STAT3 pathway, resulting in the upregulation of MMP13 and C-myc, further promoting osteoclast signaling pathway activation and tumor proliferation.

From: Myeloma cell-derived CXCL7 facilitates proliferation of tumor cells and occurrence of osteolytic lesions through JAK/STAT3 pathway

Fig. 7

A, B Immunohistochemical analyses were performed to assess the expression levels of TRAP, MMP2, MMP9, and MMP13 in the femurs of mice within the OE group and the NC group. TRAP was employed for labeling osteoclasts, and the results indicated a substantial increase in the quantity of osteoclasts in the OE group. MMP2, MMP9, and MMP13 were used to mark the relevant proteins related to the activation of osteoclast signaling pathways. The observations also revealed that the expression levels of MMP2, MMP9, and MMP13 in the bone tissue of mice in the OE group were significantly elevated. In the CXCL7-OE RPMI8226 (C) and H929 (D) cell lines, the incorporation of CXCR2 inhibitors incurs a significant downregulation of the JAK/STAT3 pathway, concurrently accompanied by a significant reduction in the expression magnitudes of MMP13 and C-myc. In the CXCL7-OE RPMI8226 (E) and H929 (F) cell lines, the administration of CXCR2 inhibitors elicited a significant attenuation of the cell proliferative capacity. In the CXCL7-OE RPMI8226 (G) and H929 (H) cell lines, the incorporation of JAK1 inhibitors gave rise to a significant reduction in the expression levels of p-STAT3, MMP13, and C-myc. In the CXCL7-OE RPMI8226 (I) and H929 (J) cell lines, the administration of JAK1 inhibitors elicited a significant attenuation of the cell proliferative capacity. K TRAP staining of CXCL7-OE/NC RPMI8226 cell lines co-cultured with primary mouse BMDMs. After 6 days, the CXCL7-OE group showed a higher number of multinucleated osteoclasts, indicating that CXCL7 promotes osteoclast differentiation. L Immunofluorescence was implemented for the precise detection of TRAP and MMP13, where TRAP acted as a definitive marker of osteoclasts. The obtained results manifested that in the CXCL7-OE group, TRAP and MMP13 presented conspicuous co-localization, inferring that MMP13 assumes a crucial role in the activation of osteoclasts.

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