Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
J Cell Physiol. 2011 Mar;226(3):573-8. doi: 10.1002/jcp.22521.
Schnurri (Shn)-2 is a transcriptional modulator of bone formation and bone resorption and its deficiency causes low turnover state with higher cancellous bone mass due to the defects in osteoclasts that exceeds the defects in osteoblasts in mice. We addressed whether such low turnover of bone remodeling in Shn2 deficiency may be modulated in the absence of estrogen that induces high turnover state in vivo. Ovariectomy reduced bone mass in wild type compared to sham operated control mice and such reduction in bone mass was also observed in Shn2 deficient mice. However, due to the high levels of basal bone mass in Shn2 deficient mice, the bone mass levels after ovariectomy were still comparable to sham operated wild-type mice. Analysis indicated that estrogen depletion increased bone resorption at similar levels in wild type and Shn2 deficient mice though the basal levels of osteoclast number was slightly lower in Shn2-deficient mice. In contrast, basal levels of bone marrow cell mineralization in cultures were low in Shn2-deficeint mice while estrogen depletion increased the mineralization levels to those that were comparable to sham wild type. This indicates that Shn2-deficient mice maintain bone mass at the levels comparable to wild-type sham mice even after ovariectomy-induced bone loss and this correlates with the high levels of mineralization activity in bone marrow cells after ovariectomy.
Schnurri (Shn)-2 是骨形成和骨吸收的转录调节剂，其缺乏导致低转换状态，松质骨量增加，这是由于破骨细胞的缺陷超过了小鼠成骨细胞的缺陷。我们研究了 Shn2 缺乏症中这种低骨重塑转换是否可以在缺乏雌激素的情况下调节，因为雌激素在体内诱导高转换状态。卵巢切除术使野生型小鼠的骨量减少，与假手术对照组相比，而 Shn2 缺乏型小鼠的骨量也减少。然而，由于 Shn2 缺乏型小鼠的基础骨量较高，卵巢切除术后的骨量水平仍与假手术野生型小鼠相当。分析表明，雌激素耗竭以相似的水平增加了野生型和 Shn2 缺乏型小鼠的骨吸收，尽管 Shn2 缺乏型小鼠的破骨细胞数量的基础水平略低。相比之下，Shn2 缺乏型小鼠的骨髓细胞培养物中的基础矿化水平较低，而雌激素耗竭使矿化水平增加至与假野生型相当的水平。这表明，即使在卵巢切除术后骨丢失后，Shn2 缺乏型小鼠也能维持与野生型假手术小鼠相当的骨量，这与卵巢切除术后骨髓细胞中高水平的矿化活性相关。
