gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes.
gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes.
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DOI：
10.1038/s42003-021-02944-y
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发表时间：
2022-01-17
影响因子：
5.9
通讯作者：
Evseenko D
中科院分区：
文献类型：
--
作者：
Liu NQ;Lin Y;Li L;Lu J;Geng D;Zhang J;Jashashvili T;Buser Z;Magallanes J;Tassey J;Shkhyan R;Sarkar A;Lopez N;Lee S;Lee Y;Wang L;Petrigliano FA;Van Handel B;Lyons K;Evseenko D
长骨和椎骨的生长在出生后由长期祖细胞库维持。人们对调节成熟软骨细胞的输出和维持的分子机制知之甚少。在这里，我们证明出生后软骨细胞特异性删除转录因子 Stat3 会导致增殖严重减少，并伴有肥大、生长板融合、发育迟缓和关节软骨进行性功能障碍的迹象。这种效应是二态性的，女性比男性受到的影响更强烈。软骨细胞特异性删除 IL-6 家族细胞因子受体 gp130，激活 Stat3，表型复制 Stat3 删除； Lifr（通过 gp130 发出信号的众多共受体之一）的缺失导致了较温和的表型。这些数据定义了调节软骨细胞维持和输出的分子回路，并揭示了 IL-6 家族细胞因子在骨骼系统中的关键积极功能，对骨骼发育和再生具有直接影响。刘等人。证明 gp130/STAT3 信号传导在生长板和关节软骨中软骨细胞的发育和稳态中的作用。作者报告说，他莫昔芬诱导出生后软骨细胞中 STAT3 或 gp130 的缺失会导致软骨细胞增殖缺陷、生长板融合和发育迟缓，以及关节软骨进行性功能障碍的迹象，雌性小鼠比雄性小鼠受到的影响更严重。
Growth of long bones and vertebrae is maintained postnatally by a long-lasting pool of progenitor cells. Little is known about the molecular mechanisms that regulate the output and maintenance of the cells that give rise to mature cartilage. Here we demonstrate that postnatal chondrocyte-specific deletion of a transcription factor Stat3 results in severely reduced proliferation coupled with increased hypertrophy, growth plate fusion, stunting and signs of progressive dysfunction of the articular cartilage. This effect is dimorphic, with females more strongly affected than males. Chondrocyte-specific deletion of the IL-6 family cytokine receptor gp130, which activates Stat3, phenocopied Stat3-deletion; deletion of Lifr, one of many co-receptors that signals through gp130, resulted in a milder phenotype. These data define a molecular circuit that regulates chondrogenic cell maintenance and output and reveals a pivotal positive function of IL-6 family cytokines in the skeletal system with direct implications for skeletal development and regeneration. Liu et al. demonstrate the role of gp130/STAT3 signalling in the development and homeostasis of chondrocytes in the growth plate and articular cartilage. The authors report that tamoxifen-induced deletion of STAT3 or gp130 in chondrocytes after birth results in defective chondrocyte proliferation, growth plate fusion and stunting, and signs of progressive dysfunction of the articular cartilage, with female mice more strongly affected than males.
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影响因子：
1.6
作者：
Ai G;Shao X;Meng M;Song L;Qiu J;Wu Y;Zhou J;Cheng J;Tong X
通讯作者：
Tong X
影响因子：
21.3
作者：
Flores A;Schell J;Krall AS;Jelinek D;Miranda M;Grigorian M;Braas D;White AC;Zhou JL;Graham NA;Graeber T;Seth P;Evseenko D;Coller HA;Rutter J;Christofk HR;Lowry WE
通讯作者：
Lowry WE
影响因子：
3
作者：
GOWER, JC
通讯作者：
GOWER, JC
影响因子：
5.6
作者：
Alberton, Paolo;Dugonitsch, Hans Christian;Aszodi, Attila
通讯作者：
Aszodi, Attila
影响因子：
2.9
作者：
Di Domenico F;Casalena G;Sultana R;Cai J;Pierce WM;Perluigi M;Cini C;Baracca A;Solaini G;Lenaz G;Jia J;Dziennis S;Murphy SJ;Alkayed NJ;Butterfield DA
通讯作者：
Butterfield DA