17beta-Estradiol overcomes human myeloma RPMI8226 cell suppression of growth, ALP activity, and mineralization in rat osteoblasts and improves RANKL/OPG balance in vitro.
Multiple myeloma (MM) is a plasma cell malignancy characterized by a high capacity to induce osteolytic bone lesions. MM patients with osteolytic bone lesions have lower numbers of osteoblasts and decreased bone formation, which plays a critical role in the bone-destructive process. Although the mechanism of estrogen action on bone cells and myeloma cells has been widely investigated, estrogen action on bone cells in MM is unknown. In this study, the effects of the gonadal hormone 17beta-estradiol on cell growth, alkaline phosphatase (ALP) activity, mineralization capacity, and RANKL/OPG ratios in primary rat osteoblasts cultured with MM cell conditioned medium (CM) or co-cultured with RPMI8226 cells were investigated. Treatments of 10(-2) to 10 nM 17beta-estradiol reversed inhibition of proliferation and ALP activity of osteoblasts by myeloma cells in a dose-dependent manner, and 10(-2) to 1 nM 17beta-estradiol reversed inhibition of the mineralization capacity of osteoblasts by myeloma cells. In co-culture experiments with primary rat osteoblasts and myeloma cells, treatments of 10(-2) to 10 nM 17beta-estradiol down-regulated transcription and secretion of RANKL and up-regulated transcription and secretion of OPG in the osteoblasts, reversing the effects of co-cultured myeloma cells. These findings suggest that 17beta-estradiol may temper the inhibitory effects of myeloma cells on osteoblasts and improve RANKL/OPG balance, providing a new agent for treatment of bone disease in myeloma.
Li
Qiubai
Q
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yu
Ke
K
Tian
Xiaolong
X
Kong
Fancong
F
You
Yong
Y
Chen
Zhichao
Z
Zou
Ping
P
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002113:Calcification, Physiologic; D002455:Cell Division / Q000187:drug effects*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D009101:Multiple Myeloma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017077:Culture Media, Conditioned; D017931:DNA Primers; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D004958:Estradiol; D000469:Alkaline Phosphatase