Finkelman R D, Bell N H, Strong D D, Demers L M, Baylink D J
Department of Periodontics, Loma Linda University, CA.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12190-3. doi: 10.1073/pnas.89.24.12190.
Previous work showed that production of transforming growth factor beta (TGF-beta) by osteoblast-like rat UMR 106 cells was increased by 17 beta-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-beta in rat long bones, female Sprague-Dawley rats were either sham-operated (n = 19) or ovariectomized (n = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25-dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from sham-operated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of TGF-beta in bone but did not change the concentration of insulin-like growth factors I or II compared with values in bone from control animals. The reduction of bone TGF-beta was evident 6 weeks after surgery but not at 3 weeks. Treatment of ovariectomized rats with estrogen eliminated the TGF-beta deficit. To determine whether 17 beta-estradiol increased TGF-beta production by normal bone cells, mouse osteoblasts were treated for 2 days with 17 beta-estradiol. The production of TGF-beta was increased almost 2-fold by 1 nM 17 beta-estradiol, and short-term treatment stimulated the intracellular accumulation of TGF-beta 1 mRNA. We conclude that ovariectomy reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could play a role in the pathogenesis of bone loss, fractures, and microfractures that occur in estrogen-deficient states. Our results support the possibility that estrogen and bone TGF-beta may be necessary for normal maintenance of the skeleton in female rats.
先前的研究表明，生理浓度的17β-雌二醇可使大鼠成骨样UMR 106细胞中转化生长因子β（TGF-β）的生成增加。为了确定卵巢切除术是否会改变大鼠长骨中TGF-β的浓度，将雌性斯普拉格-道利大鼠分为假手术组（n = 19）或卵巢切除组（n = 19），成对喂食半合成饮食6周后处死。取出胫骨干和股骨干并通过脱矿质法进行提取。卵巢切除术降低了血清雌激素水平；未改变体重、血清镁或血清1,25-二羟基维生素D水平；仅使血清钙和磷浓度产生了适度差异。与假手术组大鼠的骨骼相比，卵巢切除组大鼠骨骼中的羟脯氨酸含量更高，可提取蛋白含量更低；两组动物的钙含量无差异。与对照动物骨骼中的值相比，卵巢切除术降低了骨骼中TGF-β的浓度，但未改变胰岛素样生长因子I或II的浓度。术后6周时骨骼TGF-β的降低明显，但3周时未出现降低。用雌激素治疗卵巢切除组大鼠可消除TGF-β的不足。为了确定17β-雌二醇是否会增加正常骨细胞中TGF-β的生成，将小鼠成骨细胞用17β-雌二醇处理2天。1 nM 17β-雌二醇使TGF-β的生成增加了近2倍，短期处理刺激了TGF-β1 mRNA的细胞内积累。我们得出结论，卵巢切除术会减少大鼠骨骼中TGF-β的沉积，而骨骼中TGF-β的减少可能在雌激素缺乏状态下发生的骨质流失、骨折和微骨折的发病机制中起作用。我们的结果支持雌激素和骨骼TGF-β可能是雌性大鼠骨骼正常维持所必需的这一可能性。
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