Pignatti Emanuele, Jiang Lijie, Shah Manasvi S, Karpurapu Anish, Miao Ji, Liu Yangyang, Berber Mesut, Kalagara Roshini, Butler Aisling E, Skalnik David G, Rosen Vicki, Breault David T, Carlone Diana L
Division of Endocrinology, Boston Children's Hospital, Boston, MA, 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
Division of Endocrinology, Boston Children's Hospital, Boston, MA, 02115, USA.
Dev Biol. 2025 Sep 5;528:204-215. doi: 10.1016/j.ydbio.2025.09.004.
The mechanisms mediating endochondral bone formation remain incompletely understood. Here, we show that CXXC Finger Protein 1 (CFP1) is required for the onset of chondrogenesis during forelimb development. CFP1-deficient mesenchymal progenitor cells (LMPs) retain an immature molecular signature with elevated FGF and SHH signaling and repressed BMP signaling, in part, due to (1) reduced expression of type I BMP receptors, (2) reduced Smad1 protein levels and (3) an altered extracellular niche. Moreover, the addition of exogenous BMP ligand or antagonism of heparan sulfate restores LMP differentiation toward a chondrogenic fate and enhances BMP signaling, suggesting a defect in BMP ligand bioavailability mediates the CFP1-deficient LMP phenotype. Together, these findings define CFP1 as a gatekeeper between the undifferentiated and differentiated state of LMPs during endochondral bone formation and as a physiological regulator of BMP signaling. CLASSIFICATION: Biological Sciences.
介导软骨内成骨的机制仍未完全明确。在此，我们表明CXXC指蛋白1（CFP1）是前肢发育过程中软骨形成起始所必需的。CFP1缺陷的间充质祖细胞（LMPs）保留了不成熟的分子特征，伴有FGF和SHH信号升高以及BMP信号受到抑制，部分原因是：（1）I型BMP受体表达降低；（2）Smad1蛋白水平降低；（3）细胞外微环境改变。此外，添加外源性BMP配体或拮抗硫酸乙酰肝素可恢复LMP向软骨形成命运的分化，并增强BMP信号，表明BMP配体生物利用度缺陷介导了CFP1缺陷的LMP表型。总之，这些发现将CFP1定义为软骨内成骨过程中LMP未分化和分化状态之间的守门人以及BMP信号的生理调节因子。分类：生物科学。
