Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombo spondin-2-null mice
Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombo spondin-2-null mice
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DOI：
10.1016/j.matbio.2005.05.008
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发表时间：
2005-08-01
期刊：
影响因子：
6.9
通讯作者：
Bornstein, P
中科院分区：
文献类型：
--
作者：
Hankenson, KD;James, IE;Bornstein, P
尽管骨骼主要由细胞外基质（ECM）组成，但ECM在调节雌激素丢失引起的骨重建中所发挥的动态作用相对未被探索。先前的研究表明，缺乏基质细胞蛋白血小板反应蛋白-2（TSP 2-null）的小鼠会形成过量的皮质内骨;因此，我们假设增强TSP 2-null小鼠的骨形成可以防止卵巢切除术（OVX）诱导的骨丢失。野生型（WT）OVX小鼠表现出股骨中段皮质骨和胫骨近端骨小梁的显著损失，但OVX没有显著改变TSP 2缺失骨。TSP 2缺失小鼠显示骨形成增加，如OVX后两周血清骨钙素增加70%和OVX后五周骨形成率（BFR）增加两倍所示，如通过动态组织形态计量学测量的。WT动物在两周时血清骨钙素仅增加20%，而在五周时BFR无变化。TSP 2缺失OVX小鼠骨形成的增加伴随着骨祖细胞数量的三倍增加。尽管这些结果提供了OVX后骨几何形状维持的部分解释，但OVX后5周的TSP 2缺失小鼠也显示出比OVX WT小鼠显著更低的骨吸收水平，如通过I型胶原的氨基末端端肽（NTx）的血清水平所确定的。我们的结论是，TSP 2的情况下，保护对OVX诱导的骨丢失的两个互补的过程：增加形成和减少再吸收。(C)2005年Elsevier B. V./国际矩阵生物学学会。All rights reserved.
Although bone is composed primarily of extracellular matrix (ECM), the dynamic role that the ECM plays in regulating bone remodeling secondary to estrogen loss is relatively unexplored. Previous studies have shown that mice deficient in the matricellular protein thrombospondin-2 (TSP2-null) form excess endocortical bone; thus, we postulated that enhanced bone formation in TSP2-null mice could protect against ovariectomy (OVX)-induced bone loss. Wild-type (WT) OVX mice showed a significant loss of both midfemoral endocortical and proximal tibial trabecular bone, but OVX did not significantly alter TSP2-null bone. TSP2-null mice showed an increase in bone formation, as indicated by a 70% increase in serum osteocalcin two weeks post OVX and a two-fold increase in bone formation rate (BFR) five weeks post OVX as measured by dynamic histomorphometry. WT animals showed only a 20% increase in serum osteocalcin at two weeks and no change in BFR at five weeks. This increase in bone formation in TSP2-null OVX mice was accompanied by a three-fold increase in osteoprogenitor number. Although these results provide a partial explanation for the maintenance of bone geometry post-OVX, TSP2-null mice five weeks post-OVX also showed a significantly lower level of bone resorption than OVX WT mice, as determined by serum levels of the amino-terminal telopeptide of type I collagen (NTx). We conclude that the absence of TSP2 protects against OVX-induced bone loss by two complementary processes: increased formation and decreased resorption. (C) 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved.