Parathyroid Hormone‐Related Protein Is Required for Normal Intramembranous Bone Development
Parathyroid Hormone‐Related Protein Is Required for Normal Intramembranous Bone Development
复制标题
正常膜内骨发育需要甲状旁腺激素相关蛋白
DOI：
10.1359/jbmr.2001.16.12.2182
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发表时间：
2001
影响因子：
6.2
通讯作者：
V. Hammond
中科院分区：
文献类型：
--
作者：
N. Suda;O. Baba;N. Udagawa;T. Terashima;Y. Kitahara;Y. Takano;T. Kuroda;P. Senior;F. Beck;V. Hammond
众所周知，甲状旁腺激素相关蛋白(PTHrP)调节软骨细胞分化和软骨内骨形成。除了对软骨的作用外，成骨细胞中还发现了PTHrP及其主要受体(I型PTH/PTHrP受体)，提示PTHrP在膜内骨形成过程中起重要作用。为了阐明这个问题，我们对纯合PTHrP基因敲除小鼠的膜内骨化进行了组织学研究。我们还分析了体外和体内成骨细胞和破骨细胞的表型标志物。野生型小鼠有组织良好的分枝和吻合模式。相反，在新生的纯合子突变小鼠的下颌骨和股骨的骨领中，发现骨小梁的分支模式明显紊乱，成骨细胞排列不规则。原位杂交显示野生型小鼠骨表面大部分成骨细胞和纯合子小鼠部分不规则排列的成骨细胞表达骨钙素。杂合突变小鼠(+/？)和野生型小鼠(+/？)混合培养的原代成骨细胞碱性磷酸酶(ALP)活性和骨桥蛋白信使RNA(MRNA)的表达没有显著差异。小鼠)和来自纯合突变小鼠的基因。而纯合子突变小鼠成骨细胞中骨钙素的mRNA和蛋白水平均低于+/？小鼠，和外源PTHrP治疗纠正了这种抑制。破骨细胞和褶皱边缘形成的特征标记的免疫组织化学定位在不同的基因型间没有差异。纯合子突变小鼠颅骨成骨细胞和脾细胞共培养产生的抗酒石酸酸性磷酸酶阳性(TRAP+)单核和多核细胞数量与+/？这表明在纯合子突变小鼠中破骨细胞分化没有受到损害。这些结果表明，PTHrP不仅是调节软骨形成所必需的，也是正常膜内骨发育所必需的。
It is well established that parathyroid hormone‐related protein (PTHrP) regulates chondrocytic differentiation and endochondral bone formation. Besides its effect on cartilage, PTHrP and its major receptor (type I PTH/PTHrP receptor) have been found in osteoblasts, suggesting an important role of PTHrP during the process of intramembranous bone formation. To clarify this issue, we examined intramembranous ossification in homozygous PTHrP‐knockout mice histologically. We also analyzed phenotypic markers of osteoblasts and osteoclasts in vitro and in vivo. A well‐organized branching and anastomosing pattern was seen in the wild‐type mice. In contrast, marked disorganization of the branching pattern of bone trabeculae and irregularly aligned osteoblasts were recognized in the mandible and in the bone collar of the femur of neonatal homozygous mutant mice. In situ hybridization showed that most of the osteoblasts along the bone surfaces of the wild‐type mice and some of the irregularly aligned osteoblastic cells in the homozygous mice expressed osteocalcin. Alkaline phosphatase (ALP) activity and expression of osteopontin messenger RNA (mRNA) in primary osteoblastic cells did not show significant differences between cultures derived from the mixture of heterozygous mutant and wild‐type mice (+/? mice) and those from homozygous mutant mice. However, both mRNA and protein levels of osteocalcin in the osteoblastic cells of homozygous mutant mice were lower than those of +/? mice, and exogenous PTHrP treatment corrected this suppression. Immunohistochemical localization of characteristic markers of osteoclasts and ruffled border formation did not differ between genotypes. Cocultures of calvarial osteoblastic cells and spleen cells of homozygous mutant mice generated an equivalent number of tartrate‐resistant acid phosphatase‐positive (TRAP+) mononuclear and multinucleated cells and of pit formation to that of +/? mice, suggesting that osteoclast differentiation is not impaired in the homozygous mutant mice. These results suggest that PTHrP is required not only for the regulation of cartilage formation but also for the normal intramembranous bone development.
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DOI：
10.1210/jcem.83.8.5047
发表时间：
1998-08
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
H. Plotkin;C. Gundberg;M. Mitnick;A. F. Stewart;A. F. Stewart
通讯作者：
H. Plotkin;C. Gundberg;M. Mitnick;A. F. Stewart;A. F. Stewart
影响因子：
10.5
作者：
KARAPLIS, AC;LUZ, A;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
影响因子：
4.8
作者：
Lanske, B;Divieti, P;Kronenberg, HM
通讯作者：
Kronenberg, HM
影响因子：
56.9
作者：
JUPPNER, H;ABOUSAMRA, AB;SEGRE, GV
通讯作者：
SEGRE, GV