Relationship between abnormal osteoblasts and cellular immunity in multiple myeloma

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Abstract

Bone destruction and abnormal immunity always occur in patients with multiple myeloma (MM), which manifested by impaired osteoblasts and immune system. In this study, we investigated the quantity and function of osteoblasts by co-culture, the status of cellular immunity by flow cytometry, and the relationship between them in MM patients. The results showed that the numbers and function of osteoblasts in MM patients were lower than those in normal controls. Bortezomib could increase the numbers, calcium depositions and the expression of Bone morphogenetic protein-2 (BMP-2) mRNA of osteoblasts from MM patients in vitro. The status of cellular immunity in MM patients was abnormal, including decreased ratio of CD4+/CD8+, DC1/DC2 and Th1/Th2, and increased ratio of regulatory T cells. The ratio of CD4+/CD8+(r = 0.685) and CD4+CD25+/CD3+T(r = 0.568) were positively correlated with the quantity of osteoblasts (both P < 0.05). The serum interleukin-7(IL-7) level of MM patients was higher than that of normal controls (2.07 ± 0.71 vs. 1.62 ± 0.15 ng/L, P < 0.05), and was negatively correlated with the quantity of osteoblasts (r = -0.682, P < 0.01). Our data indicated that the proliferation and osteogenic potential of osteoblasts in MM patients were decreased which could be recovered by bortezomib in vitro. The down-regulation of cellular immunity was correlated with the quantity of osteoblasts.

Figures

  • Figure 1 Osteoblasts. (a,b) The quantity of osteoblasts from MM patients was less than that of normal controls under the inverted microscope. (c) The quantity of osteoblasts from MM patients was less than that of normal controls (*P <0.01). After co-cultured with MM patient serum, the quantity of osteoblasts from MM patients was less than that of normal controls (**P < 0.05). And the quantity of normal osteoblasts co-cultured with MM patient serum was less than that of normal osteoblasts (**P < 0.05).
  • Figure 2 Von Kossa staining. (a,b) The depositions of MM patients were less than those of normal controls tested by Von Kossa staining. (c) The depositions of MM patients was less than those of normal controls (*P < 0.01). The calcium depositions in MM osteoblasts with bortezomib were more than those without bortezomib (*P < 0.01), less than those in normal controls (*P < 0.01).
  • Figure 3 Cellular immunity. In MM patients, (a) the ratio of CD4+/CD8+, DC1/DC2 and the Th1/Th2 were significantly decreased (all P < 0.05); the ratio of CD8+CD25+/CD3+T were reduced, meanwhile that of CD4+CD25+/CD3+T and CD4+CD25+CD127low/CD4+T were significantly increased (all P < 0.05). (b) The serum IL-7 level of MM patients was higher than that of normal controls (*P < 0.05).
  • Figure 4 Changes of the osteoblasts after cultured with bortezomib. (a) After co-cultured with bortezomib, the quantity of osteoblasts from MM patients was more than those without bortezomib (*P < 0.05). (b) The expressions of BMP2 mRNA were detected by RT-PCR. The BMP2 expression of osteoblasts from MM patient (line a,c) was negative. The BMP2 expression of osteoblasts from normal controls (line b) and that of osteoblasts from MM patient co-cutured with Bortezomib (line d), were both positive.

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APA

Fu, R., Gao, S., Peng, F., Li, J., Liu, H., Wang, H., … Shao, Z. (2014). Relationship between abnormal osteoblasts and cellular immunity in multiple myeloma. Cancer Cell International, 14(1). https://doi.org/10.1186/1475-2867-14-62

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