An Investigation On The Anabolic Effect Of Parathyroid Hormone

An Investigation on the Anabol ic Effectof Parathyroid HormoneAbstractThe widely used therapeutic agents for osteoporosis are inhibitors of bone resorption to date, which can prevent bone loss but only have very limited effect in raising bone mass. Parathyroid hormone (PTH) and certain of its fragments are considered as one of the most promising anabolic agents, 3-month-old or younger rats were commonly used in previous years in experiments focusing on the anabolic effect of PTH, to testify the anabolic effect of intermittent injection of PTH in rats which are middle-aged and long after estrogen depletion (this state is similar to postmenopausal women long after menopause) and probe into the mechanisms of the anabolic effect of PTH in cellular and molecular levels, we have completed following investigations.1.The effect of intermittent injection of recombinant human parathyroid hormone (1-84) (rhPTH1?4) on bone mineral density and histomorphometry of ovariectomized rats.6-month-old virgin female Sprague-Dawley rats were randomly divided into 5 groups; (TD Ovariectornized for end point (OVXE, n6) , ~Ovariectomized for PTH treatment (OVXE +PTH, n ?6) , Sham-operated for end (ShamE, n 6), ?Sham-operated for baseline (ShamB, n 5) , ?Ovariectomized for baseline (OVXB, n 6). The lumbar and proximal femur bone mineral density (BMD) was measured by dual energy X-ray absorptiometry prior to operation, 3 and 4. 5 months after operation in OVXE, OVXE-I-PTH and ShamE rats. during 3 ?. 5 months postovariectomy, OVXE + PTH rats received daily subcutaneous injection of rhPTI-3[1?4 (20?tg/lOOg BW,6 times/week), OVXE and ShamE received injection of vehicle;OVXE, OVXE+PTH and ShamE rats at 4. 5 months, ShamB andOVXB rats at 3 months postovariectomy were sacrificed, theproximal tibiae were processed for histomorphometry, calcein wasadministered intraperitoneally at 6 and 2 day prior to killing to labelthe mineralizing surfaces of bone. The results showed that @thelumbar BMD of OVXE rats at 3 and 4. 5 months postovariectomychangPd little (both P > 0. 05 ) 3 the percent trabecular area (%TbAr) was significantly lower and the percent labeled perimeter (%LPm), mineral apposition rate(MAR), osteoclast number(N of Oc)were a1l higher in OVXB than those of ShamB(P<0. 00l, 0. 05, 0.05, and 0. 01 respectively). @During PTH/vehicle injection period,the lumbar BMD in OVXE +PTH had increased 15. 7 I 9. 5mg/cm'(X f SD), which was similar to that of ShamE (P> 0. 05 ), whilethat of OVXE has decreasd 13. 8i 8. 8mg/cm', the changes betweenany OVXE+PTH and OVXE were significant(Pr0. 01 ); the BMDof proximal femur in OVXE, OVXE + PTH and ShamE hadsimu1taneously increased (P> 0. 05 between two groups), @Bonehistomorphometry analysis showed that the %TbAr of OVXE+PTHwas higher than that of OVXE (Pr 0. 05) and similar to that ofOVXB(P>0. 05) l the TbTh of OVXE+PTH was higher than anyother group (P r 0. 05 ), the TbN of OVXE + PTH was s1ightlygreater than that of OVXE (0. 05XPr 0. 01 ), the %LPm, MARand BFR/BV of OVXE+PTH were all higher than that of OVXEand ShamE (P< 0. 01 or less), N of OC was not different amongOVXE, OVXE+PTH and ShamE. These results suggest thatrotheresponse of lumbar BMD to ovariectomy is not sensitive as tibiametaphysis %TbAr in 6--month-0ld SD rat, ovariectomy could notinfluence the BMD of cortical bone and may raise both osteoblasticand osteoclastic activity at least in 3 months after operationl @rhPTH,-,. can significantly increase the lumbar BMD, maintain thetrabecular area in tibial metaphysis and has no effect on femoral. 7.cortical BMD in ovariectomized rats3 @ Intermittent treatment ofPTH can promote the osteoblastic activity without influence onosteoclastic activity, this therapy increases bone mass mainly by.. Pincreasing rbTh, although it can slight1y raise TbN.2. The Effcct of PTH on the ProIiferation and AnaboIic Function ofCultured Rat OsteoblastsWe have set a cell culture...