Sex-Linked Skeletal Phenotype of Lysyl Oxidase Like-1 Mutant Mice.
Sex-Linked Skeletal Phenotype of Lysyl Oxidase Like-1 Mutant Mice.
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DOI：
10.1007/s00223-015-0076-4
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发表时间：
2016-03
影响因子：
4.2
通讯作者：
Trackman PC
中科院分区：
文献类型：
--
作者：
Alsofi L;Daley E;Hornstra I;Morgan EF;Mason ZD;Acevedo JF;Word RA;Gerstenfeld LC;Trackman PC
赖氨酸氧化酶是胶原蛋白和弹性蛋白交联以及包括骨在内的细胞外基质成熟所必需的。赖氨酸氧化酶家族由赖氨酸氧化酶（LOX）和4个异构体（LOXL1-4）组成。在这里，我们研究LOXL1的缺失是否会导致骨骼异常，LOXL1主要与弹性蛋白成熟有关。采用微计算机断层扫描（μCT）对13周龄野生型（WT）和LOXL1−/−雄性和雌性小鼠的左股骨（n=8）、L5椎骨（n=8）和胫骨（n=8）进行分析。对右股骨（n=8）进行LOXL1免疫组化，并对破骨细胞和生长板进行组织化学/组织学分析。对所有小鼠的血清进行骨转换标志物分析。结果表明，LOXL1在野生型股骨生长板中表达强烈。与WT相比，雌性突变小鼠的长骨和椎骨的骨小梁结构明显恶化。雌性突变小鼠的BV/TV、Conn.D、股骨远端干骺端骨小梁厚度和数量下降，而雄性突变小鼠则没有。雌性突变小鼠股骨小梁间距明显增加。雌性突变小鼠L5椎骨小梁的研究结果相似。与WT雌性小鼠相比，雌性突变小鼠骨小梁表面TRAP阳性破骨细胞数量增加，与血清RANKL升高和OPG水平降低一致。骨转换标记物分析证实，与野生型小鼠相比，雌性LOXL1 - / -小鼠血清中CTX-1显著升高，表明骨吸收增加；血清中PINP水平降低，表明骨形成减少。小天狼星红染色仅显示雌性LOXL1−/−小鼠胶原组织的异质性丧失，几乎没有黄色和橙色双折射。雌性和雄性LOXL1 - / -小鼠的软骨细胞柱组织也受到损伤，但雌性损伤程度更大。数据表明，LOXL1 - / -突变小鼠出现了以骨体积分数减少和小梁结构受损为特征的尾轴和轴向骨骼表型，主要发生在雌性小鼠中。
Lysyl oxidases are required for collagen and elastin cross-linking and extracellular matrix maturation including in bone. The lysyl oxidase family consists of lysyl oxidase (LOX) and 4 isoforms (LOXL1–4). Here we investigate whether deletion of LOXL1, which has been linked primarily to elastin maturation, leads to skeletal abnormalities. Left femurs (n=8), L5 vertebrae (n=8) and tibiae (n=8) were analyzed by micro-computed tomography (μCT) in 13-week old wild type (WT) and LOXL1−/− male and female mice. Right femurs (n=8) were subjected to immunohistochemistry for LOXL1, and histochemical/histology analyses of osteoclasts and growth plates. Sera from all mice were analyzed for bone turnover markers. Results indicate strong expression of LOXL1 in wild type growth plates in femurs. Significant deterioration of trabecular bone structure in long bones and vertebrae from female was observed in not from male, mutant mice compared with WT. Decreases in BV/TV, Conn.D, and trabecular thickness and number in the femoral distal metaphysis were observed in female, but not male, mutant mice. Trabecular spacing was increased significantly in femurs of female mutant mice. Findings were similar in trabeculae of L5 vertebrae from female mutant mice. The number of TRAP positive osteoclasts at the trabecular bone surface was increased in female mutant mice compared with WT females, consistent with increased serum RANKL and decreased OPG levels. Analysis of bone turnover markers confirmed increased bone resorption as indicated by significantly elevated CTX-1 in the serum of female LOXL1−/− mice compared to their wild-type counterparts, as well as decreased bone formation as measured by decreased serum levels of PINP. Picrosirius red staining revealed a loss of heterogeneity in collagen organization in female LOXL1−/− mice only, with little to no yellow and orange birefringence. Organization was also impaired in chondrocyte columns in both female and male LOXL1−/− mice, but to a greater extent in females. Data indicate that LOXL1−/− mutant mice develop appendicular and axial skeletal phenotypes characterized by decreased bone volume fraction and compromised trabecular microstructure, predominantly in females.
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影响因子：
4.8
作者：
Atsawasuwan, Phimon;Mochida, Yoshiyuki;Yamauchi, Mitsuo
通讯作者：
Yamauchi, Mitsuo
影响因子：
4.1
作者：
Bord, S;Ireland, DC;Compston, JE
通讯作者：
Compston, JE
影响因子：
4.3
作者：
Gualeni, Benedetta;Rajpar, M. Helen;Briggs, Michael D.
通讯作者：
Briggs, Michael D.
影响因子：
3.7
作者：
Khosravi R;Sodek KL;Xu WP;Bais MV;Saxena D;Faibish M;Trackman PC
通讯作者：
Trackman PC
影响因子：
4
作者：
Ballanti, P;Minisola, S;Bonucci, E
通讯作者：
Bonucci, E