Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
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DOI：
10.1371/journal.pone.0011492
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发表时间：
2010-07-09
期刊：
影响因子：
3.7
通讯作者：
Westendorf JJ
中科院分区：
文献类型：
--
作者：
Razidlo DF;Whitney TJ;Casper ME;McGee-Lawrence ME;Stensgard BA;Li X;Secreto FJ;Knutson SK;Hiebert SW;Westendorf JJ
组蛋白去乙酰化酶（Hisp）3是一种有助于表观遗传编程的核酶，是胚胎发育所必需的。为了确定Hdac 3在骨形成中的作用，我们将Hdac 3外显子7周围具有loxP位点的小鼠与在osterix启动子控制下表达Cre重组酶的小鼠杂交。由此产生的Hdac 3条件性基因敲除（CKO）小鼠发育不良，并且在膜内和软骨内骨形成方面存在严重缺陷。由于骨小梁数量大幅减少，Hdac 3 CKO小鼠的颅骨显著变薄，股骨远端的骨小梁体积减少75%。与野生型或杂合子同窝出生的小鼠相比，HDac 3-CKO小鼠的成骨细胞较少，骨髓脂肪细胞占组织面积的比例较多。骨形成率在Hdac 3 CKO股骨的皮质和骨小梁区域均受到抑制。微阵列分析显示，许多发育信号通路受到Hdac 3缺陷的影响。因此，表达osterix的祖细胞中的Hdac 3缺失干扰骨形成并促进骨髓脂肪细胞分化。这些结果表明Hdac 3抑制对骨骼健康有害。
Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health.
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影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
5.3
作者：
Guenther, MG;Barak, O;Lazar, MA
通讯作者：
Lazar, MA
影响因子：
6.2
作者：
Bellosta, P;Masramon, L;Basilico, C
通讯作者：
Basilico, C
影响因子：
10.5
作者：
Guenther, MG;Yu, JJ;Lazar, MA
通讯作者：
Lazar, MA
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B