It is well known that parathyroid hormone (PTH) possesses an anabolic effect on bone. However, the mechanisms are not fully elucidated. So far, it is unclear whether or not PTH could stimulate the expression of bone morphogenetic protein-2 (BMP-2), a strong mediator for bone formation. Growing evidence suggests that BMP-2 expression is regulated by the mevalonate pathway and Rho-associated protein kinase (ROK) activity. This study was performed to examine if PTH affects BMP-2 expression and to clarify its involvement of the mevalonate pathway. Osteoblastic MC3T3-E1 cells were treated with human PTH-(1-34) to determine BMP-2 mRNA expression levels by real-time PCR and to measure the ROK activity by the kinase assay. Incubation with 10 (-9)-10 (-8) M of hPTH-(1-34) for 6 h induced significant upregulation of BMP-2 mRNA levels in MC3T3-E1 cells. Short-term treatment of hPTH-(1-34) suppressed Rho kinase activity and mevalonate kinase mRNA levels. PTH-induced BMP-2 mRNA upregulation was selectively reversed by geranylgeranyl pyrophosphate (GGPP) pretreatment, but not by mevalonate pretreatment. These findings suggest that BMP-2 mRNA expression was upregulated by PTH in MC3T3-E1 cells mediated by mevalonate pathway suppression followed by ROK inhibition. We have now demonstrated for the first time that PTH stimulated BMP-2 mRNA expression via the mevalonate pathway and ROK in osteoblastic MC3T3-E1 cells.
Background/Aims: Serum parathyroid hormone (PTH) concentration provides a rough index of the severity of secondary hyperparathyroidism (SHPT) due to chronic renal failure. Since serum PTH inversely related to calcium (Ca) level, we attempted to create a new index based on the relationship. Methods: Our subjects were 70 patients undergoing maintenance hemodialysis (HD) in a single facility. Using multiple pairs of serum Ca corrected for albumin (cCa) and intact PTH (iPTH) values drawn simultaneously, we determined the steepest slope of cCa-iPTH relationship for each individual patient to get a line closely resembling the cCa-PTH sigmoidal curve. Results: Based on the slopes, the following equation was obtained: iPTH2 = iPTH1 + (cCa1 – cCa2) × (43 + 0.47 × iPTH1), where the PTH values at any 2 arbitrary values of cCa1 and cCa2 were assumed to be iPTH1 and iPTH2, respectively. When ‘corrected PTH’ is defined as the predicted value of iPTH at cCa = 9.0 mg/dl, its correlation was better than iPTH with the total volume of the parathyroid glands estimated by ultrasonography. Similar results were found in 30 parathyroidectomized patients at other facilities. Conclusion: ‘Corrected PTH’ may represent a useful parameter for assessing the severity of SHPT from single determinations of cCa and iPTH drawn at the same time.
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