The effect of bovine parathyroid hormone withdrawal on MC3T3-E1 cell proliferation and phosphorus metabolism

PLoS One. 2015 Mar 16;10(3):e0120402. doi: 10.1371/journal.pone.0120402. eCollection 2015.

Abstract

Hypocalcemia and hypophosphatemia are common complications after parathyroidectomy (PTX). Sudden removal of high circulating levels of parathyroid hormone (PTH) causes decreased osteoclastic resorption resulting in a decreased bone remodeling space. These phenomena are likely due to an increased influx of calcium and phosphorus into bone. However, there are currently no data to support this hypothesis. In this study, we found that PTX significantly reduced levels of PTH, calcium and phosphate. Compared with preoperative levels, after 1 year, postoperative PTH, calcium and phosphate levels were 295.6 ± 173.7 pg/mL (P < 0.05), 86.62 ± 15.98 mg/dL (P < 0.05) and 5.56 ± 2.03 mg/dL (P < 0.05), respectively. We investigated continuous bovine PTH administration as well as withdrawal of bovine PTH stimulation in the mouse osteoblast precursor cell line MC3T3-E1. MC3T3-E1 cells were cultured with continuous bovine PTH treatment for 20 days or with transient bovine PTH treatment for 10 days. High doses of continuous bovine PTH exposure strongly reduced cell proliferation, alkaline phosphatase activity and the number of mineralized calcium nodules. However, withdrawal of bovine PTH (100 ng/mL) significantly increased the number of mineralized calcium nodules and caused a rapid decline in calcium and phosphorus content of culture medium. In conclusion, continuous exposure to bovine PTH inhibited osteoblast differentiation and reduced the formation of mineralized nodules. However, this inhibition was removed and mineralized nodule formation resumed with withdrawal of bovine PTH. According to the results of our clinical examinations and in vitro experiments, we hypothesize that the sudden removal of high levels of PTH may cause an increased influx of calcium and phosphorus into bone after PTX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase / metabolism
  • Animals
  • Calcification, Physiologic / drug effects
  • Calcium / metabolism
  • Cattle
  • Cell Line
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism*
  • Parathyroid Hormone / analogs & derivatives*
  • Parathyroid Hormone / pharmacology
  • Parathyroidectomy / adverse effects
  • Perioperative Period
  • Phosphorus / metabolism*

Substances

  • Parathyroid Hormone
  • parathyroid hormone, bovine
  • Phosphorus
  • Alkaline Phosphatase
  • Calcium

Grants and funding

This work was supported by Guangdong Provincial Science and Technology Foundation (No. 2012B031800164 and 2011B031800303), the National Natural Science Foundation (No. 81370808, 81270784 and 81170683), Guangzhou City Science and Technology Project (No. 12A56041537, 2012J4300084 and 2012Y2-00028), National Key Technology R&D Program (No. 2011BAI10B06), National key clinical specialist construction Programs of China, Chinese Society of Nephrology (No.14050400577) and Medical Scientific Research Foundation of Guangdong Province (No.A2014259). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.