Department of Orthopaedic Surgery, Keck School of Medicine of USC, University of Southern California (USC), Los Angeles, CA, 90033, USA.
Department of Orthopaedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, China.
Commun Biol. 2022 Jan 17;5(1):64. doi: 10.1038/s42003-021-02944-y.
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.
长骨和脊椎的生长在出生后由一个持久的祖细胞池维持。关于调节产生成熟软骨的细胞的输出和维持的分子机制知之甚少。在这里，我们证明了转录因子 Stat3 在出生后软骨细胞特异性缺失会导致增殖严重减少，同时伴有肥大增加、生长板融合、生长迟缓以及关节软骨进行性功能障碍的迹象。这种影响是二态的，女性比男性受影响更严重。IL-6 家族细胞因子受体 gp130 的软骨细胞特异性缺失会激活 Stat3，从而模拟 Stat3 的缺失；gp130 信号的许多共受体之一 Lifr 的缺失导致表型更温和。这些数据定义了一个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正向功能，对骨骼发育和再生具有直接影响。
