Phosphorylation of human calsequestrin: implications for calcium regulation

Prolactin (PRL) is known to participate in the lactation-induced maternal bone loss, presumably by inducing the release of receptor activator of nuclear factor-κB ligand (RANKL), a potent osteoclastogenic factor from osteoblasts. Since maternal bone resorption was too massive to be solely explained by RANKL and osteoclasts did not express PRL receptors (PRLR), the involvement of some other osteoblast-derived osteoclastogenic modulators was anticipated. Herein, the authors used quantitative real-time PCR to investigate the mRNA expressions of various osteoclastogenic factors in osteoblast-like UMR106 cells directly exposed to PRL for 48 h. These cells were found to express PRLR and respond to 300 ng/ml PRL by increasing RANKL mRNA expression. This PRL concentration (comparable to plasma PRL levels in lactation) also induced the upregulation of monocyte chemoattractant protein (MCP)-1, cyclooxygenase (Cox)-2, and ephrin-B1, whereas a higher concentration (500 ng/ml) was required to upregulate tumor necrosis factor (TNF)-α and interleukin (IL)-1. However, 100-500 ng/ml PRL affected neither the cell proliferation, the cell viability nor the mRNA expressions of macrophage colony-stimulating factor, IL-6, ephrin type-B receptor 4 and ephrin-B2. In conclusion, besides RANKL overexpression, PRL upregulated the expressions of other osteoclastogenic modulators, i.e., MCP-1, Cox-2, TNF-α, IL-1, and ephrin-B1, thus, further explaining how PRL induced bone loss in lactating mothers.