Connective Tissue Growth Factor Is Required for Skeletal Development and Postnatal Skeletal Homeostasis in Male Mice
Connective Tissue Growth Factor Is Required for Skeletal Development and Postnatal Skeletal Homeostasis in Male Mice
复制标题
DOI：
10.1210/en.2010-0145
复制
发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Smerdel-Ramoya, Anna
中科院分区：
文献类型：
--
作者：
Canalis, Ernesto;Zanotti, Stefano;Smerdel-Ramoya, Anna
结缔组织生长因子(CTGF)是富含半胱氨酸的61(Cyr 61)，CTGF，肾母细胞瘤过度表达(CCN)家族的成员，由成骨细胞合成，其过度表达抑制成骨细胞的形成，导致骨量减少。CTGF的全局失活会导致软骨内骨形成缺陷和围产期死亡，因此，CTGF失活对出生后骨骼的影响尚不清楚。为了研究CTGF的功能，我们通过交配CTGF条件性小鼠产生了CTGF(+/LacZ)杂合子缺失小鼠和组织特异性缺失CTGF小鼠，其中CTGF的侧翼是LOX序列，表达Cre重组酶的小鼠在配对相关的同源框基因1(PRX1)增强子(PRX1-CRE)或骨钙素启动子(Oc-CRE)的控制下。CTGF(+/LacZ)杂合子小鼠在1月龄时表现出一过性骨量减少，继发于骨小梁数量减少。在用PRX1-CRE产生的1个月大的CTGF条件性缺失雄性小鼠中也观察到了类似的骨量减少表型，这表明骨小梁数量的减少是继发于软骨内骨形成受损的。相反，当通过Oc-Cre实现CTGF的条件缺失时，仅在6个月大的雄性小鼠中观察到骨量减少的表型。CTGF杂合子或条件性缺失小鼠的成骨细胞和破骨细胞数量、骨形成和腐蚀面没有受到影响。综上所述，CTGF对正常骨骼发育是必需的，但对出生后骨骼动态平衡的影响较小。(内分泌学151：3490-3501,2010)
Connective tissue growth factor (CTGF), a member of the cysteine-rich 61 (Cyr 61), CTGF, nephroblastoma overexpressed (NOV) (CCN) family of proteins, is synthesized by osteoblasts, and its overexpression inhibits osteoblastogenesis and causes osteopenia. The global inactivation of Ctgf leads to defective endochondral bone formation and perinatal lethality; therefore, the consequences of Ctgf inactivation on the postnatal skeleton are not known. To study the function of CTGF, we generated Ctgf(+/LacZ) heterozygous null mice and tissue-specific null Ctgf mice by mating Ctgf conditional mice, where Ctgf is flanked by lox sequences with mice expressing the Cre recombinase under the control of the paired-related homeobox gene 1 (Prx1) enhancer (Prx1-Cre) or the osteocalcin promoter (Oc-Cre). Ctgf(+/LacZ) heterozygous mice exhibited transient osteopenia at 1 month of age secondary to decreased trabecular number. A similar osteopenic phenotype was observed in 1-month-old Ctgf conditional null male mice generated with Prx1-Cre, suggesting that the decreased trabecular number was secondary to impaired endochondral bone formation. In contrast, when the conditional deletion of Ctgf was achieved by Oc-Cre, an osteopenic phenotype was observed only in 6-month-old male mice. Osteoblast and osteoclast number, bone formation, and eroded surface were not affected in Ctgf heterozygous or conditional null mice. In conclusion, CTGF is necessary for normal skeletal development but to a lesser extent for postnatal skeletal homeostasis. (Endocrinology 151: 3490-3501, 2010)