Bcl-2 lies downstream of parathyroid hormone-related peptide in a signaling pathway that regulates chondrocyte maturation during skeletal development.
Bcl-2 lies downstream of parathyroid hormone-related peptide in a signaling pathway that regulates chondrocyte maturation during skeletal development.
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Bcl-2位于甲状旁腺激素相关肽的下游信号传导途径中，该途径在骨骼发育过程中调节软骨细胞的成熟。
DOI：
10.1083/jcb.136.1.205
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发表时间：
1997-01-13
影响因子：
7.8
通讯作者：
Baron, R
中科院分区：
文献类型：
--
作者：
Amling, M;Neff, L;Tanaka, S;Inoue, D;Kuida, K;Weir, E;Philbrick, WM;Broadus, AE;Baron, R
甲状旁腺素相关肽（PTHrP）似乎在骨骼发育中发挥重要作用。小鼠中PTHrP基因的靶向破坏导致骨骼发育不良，同时加速软骨细胞成熟（Amizuka，N.，H. Warshawsky，J.E.亨德森，D. Goltzman和A.C.卡拉普利斯1994. 126：1611-1623; Karaplis，A.C.，A. Luz，J. Glowacki，R. T. Bronson，V.L.J. Tybulewicz，H.M. Kronenberg和R.C.穆里根1994. Genes Dev. 8：277-289）。组成型活性突变体PTH/PTHrP受体已在詹森型人干骺端软骨发育不良（一种以骨骼成熟延迟为特征的疾病）中发现（Schipani，E.，K. Kruse和H.尤普纳。1995.科学（Wash）DC）。268：98- 100）。然而，PTHrP影响这一发育程序的分子机制仍然知之甚少。我们在这里报告，PTHrP增加Bcl-2的表达，一种蛋白质，控制程序性细胞死亡的几种细胞类型，在生长板软骨细胞在体外和体内，导致其成熟的延迟，对肥大和凋亡性细胞死亡。因此，PTHrP的过度表达的胶原II启动子的控制下，在转基因小鼠的骨骼发育的显着延迟。正如从这些结果所预期的，编码Bcl-2的基因的缺失导致软骨细胞的加速成熟和长骨的缩短。因此，Bcl-2位于PTHrP的下游，控制软骨细胞成熟和骨骼发育。
Parathyroid hormone–related peptide (PTHrP) appears to play a major role in skeletal development. Targeted disruption of the PTHrP gene in mice causes skeletal dysplasia with accelerated chondrocyte maturation (Amizuka, N., H. Warshawsky, J.E. Henderson, D. Goltzman, and A.C. Karaplis. 1994. J. Cell Biol. 126:1611–1623; Karaplis, A.C., A. Luz, J. Glowacki, R.T. Bronson, V.L.J. Tybulewicz, H.M. Kronenberg, and R.C. Mulligan. 1994. Genes Dev. 8: 277–289). A constitutively active mutant PTH/PTHrP receptor has been found in Jansen-type human metaphyseal chondrodysplasia, a disease characterized by delayed skeletal maturation (Schipani, E., K. Kruse, and H. Jüppner. 1995. Science (Wash. DC). 268:98– 100). The molecular mechanisms by which PTHrP affects this developmental program remain, however, poorly understood. We report here that PTHrP increases the expression of Bcl-2, a protein that controls programmed cell death in several cell types, in growth plate chondrocytes both in vitro and in vivo, leading to delays in their maturation towards hypertrophy and apoptotic cell death. Consequently, overexpression of PTHrP under the control of the collagen II promoter in transgenic mice resulted in marked delays in skeletal development. As anticipated from these results, deletion of the gene encoding Bcl-2 leads to accelerated maturation of chondrocytes and shortening of long bones. Thus, Bcl-2 lies downstream of PTHrP in a pathway that controls chondrocyte maturation and skeletal development.
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DOI：
10.1083/jcb.126.6.1611
发表时间：
1994-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Amizuka N;Warshawsky H;Henderson JE;Goltzman D;Karaplis AC
通讯作者：
Karaplis AC
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA
影响因子：
11.4
作者：
HARDY, MH
通讯作者：
HARDY, MH
DOI：
10.1073/pnas.88.16.6961
发表时间：
1991-08-01
影响因子：
11.1
作者：
HOCKENBERY, DM;ZUTTER, M;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
影响因子：
56.9
作者：
Lanske, B;Karaplis, AC;Kronenberg, HM
通讯作者：
Kronenberg, HM