Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation.
Expression of RMRP RNA is regulated in chondrocyte hypertrophy and determines chondrogenic differentiation.
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DOI：
10.1038/s41598-017-06809-5
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发表时间：
2017-07-25
影响因子：
4.6
通讯作者：
Welting TJM
中科院分区：
文献类型：
--
作者：
Steinbusch MMF;Caron MMJ;Surtel DAM;Friedrich F;Lausch E;Pruijn GJM;Verhesen W;Schroen BLM;van Rhijn LW;Zabel B;Welting TJM
编码RNase MRP复合体lncRNA成分的rmrp基因突变是软骨毛发育不全的起源。软骨毛发育不全与骨骼发育受损引起的严重侏儒症有关。然而，RMRP RNA突变导致骨骼发育不良的原因尚不清楚。由于生长板的软骨分化是长骨发育所必需的，我们假设RMRP RNA在软骨分化中起关键作用。在小鼠生长板和ATDC5培养物成软骨分化过程中检测到Rmrp RNA和RNase MRP蛋白亚基的表达，发现Rmrp RNA的表达与软骨细胞肥大相关。在ATDC5培养中，基因干扰Rmrp RNA表达导致软骨分化失调，对肥大、pre-rRNA加工和rRNA水平的变化有显著影响。启动子报告子研究表明Rmrp RNA表达响应软骨形成形态因子。软骨毛发育不全成纤维细胞的成软骨反分化受到损害，对肥厚分化有明显影响。总之，我们的数据表明，RMRP RNA的表达在软骨分化的不同阶段受到调节，并表明RMRP RNA可能在软骨细胞肥大中起关键作用，对CHH的病理生物学有潜在的影响。
Mutations in the RMRP-gene, encoding the lncRNA component of the RNase MRP complex, are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in RMRP RNA lead to skeletal dysplasia. Since chondrogenic differentiation of the growth plate is required for development of long bones, we hypothesized that RMRP RNA plays a pivotal role in chondrogenic differentiation. Expression of Rmrp RNA and RNase MRP protein subunits was detected in the murine growth plate and during the course of chondrogenic differentiation of ATDC5 cultures, where Rmrp RNA expression was found to be correlated with chondrocyte hypertrophy. Genetic interference with Rmrp RNA expression in ATDC5 cultures caused a deregulation of chondrogenic differentiation, with a prominent impact on hypertrophy and changes in pre-rRNA processing and rRNA levels. Promoter reporter studies showed that Rmrp RNA expression responds to chondrogenic morphogens. Chondrogenic trans-differentiation of cartilage-hair hypoplasia fibroblasts was impaired with a pronounced impact on hypertrophic differentiation. Together, our data show that RMRP RNA expression is regulated during different stages of chondrogenic differentiation and indicate that RMRP RNA may play a pivotal role in chondrocyte hypertrophy, with potential consequences for CHH pathobiology.
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影响因子：
2.7
作者：
Guo, J;Chung, UI;Kronenberg, HM
通讯作者：
Kronenberg, HM
DOI：
10.1016/0922-3371(90)90079-c
发表时间：
1990-05-01
期刊：
CELL DIFFERENTIATION AND DEVELOPMENT
影响因子：
--
作者：
ATSUMI, T;MIWA, Y;IKAWA, Y
通讯作者：
IKAWA, Y
影响因子：
4
作者：
Coleman, Cynthia M.;Vaughan, Erin E.;Barry, Frank
通讯作者：
Barry, Frank
影响因子：
5.6
作者：
Maida Y;Kyo S;Lassmann T;Hayashizaki Y;Masutomi K
通讯作者：
Masutomi K
影响因子：
64.8
作者：
Huang W;Thomas B;Flynn RA;Gavzy SJ;Wu L;Kim SV;Hall JA;Miraldi ER;Ng CP;Rigo F;Meadows S;Montoya NR;Herrera NG;Domingos AI;Rastinejad F;Myers RM;Fuller-Pace FV;Bonneau R;Chang HY;Acuto O;Littman DR
通讯作者：
Littman DR