Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
Commun Biol. 2024 Oct 23;7(1):1380. doi: 10.1038/s42003-024-07077-6.
Corin is a protease that activates atrial natriuretic peptide (ANP), a hormone in cardiovascular homeostasis. Structurally, ANP is similar to C-type natriuretic peptide (CNP) crucial in bone development. Here, we examine the role of corin and ANP in chondrocyte differentiation and bone formation. We show that in Corin and Nppa (encoding ANP) knockout (KO) mice, chondrocyte differentiation is impaired, resulting in shortened limb long bones. In adult mice, Corin and Nppa deficiency impairs bone density and microarchitecture. Molecular studies in cartilages from newborn Corin and Nppa KO mice and in cultured chondrocytes indicate that corin and ANP act in chondrocytes via cGMP-dependent protein kinase G signaling to inhibit mitogen-activated protein kinase phosphorylation and stimulate glycogen synthase kinase-3β phosphorylation and β-catenin upregulation. These results indicate that corin and ANP signaling regulates chondrocyte differentiation in bone development and homeostasis, suggesting that enhancing ANP signaling may improve bone quality in patients with osteoporosis.
卡里翁是一种激活心钠肽（ANP）的蛋白酶，后者是心血管稳态中的一种激素。在结构上，ANP 与在骨骼发育中起关键作用的 C 型利钠肽（CNP）相似。在这里，我们研究了卡里翁和 ANP 在软骨细胞分化和骨形成中的作用。我们发现，在卡里翁和 Nppa（编码 ANP）基因敲除（KO）小鼠中，软骨细胞分化受损，导致肢体长骨变短。在成年小鼠中，Corin 和 Nppa 缺乏会损害骨密度和微结构。对新生 Corin 和 Nppa KO 小鼠软骨中的分子研究和培养的软骨细胞表明，卡里翁和 ANP 通过 cGMP 依赖性蛋白激酶 G 信号在软骨细胞中发挥作用，抑制丝裂原活化蛋白激酶磷酸化，刺激糖原合酶激酶-3β磷酸化和β-连环蛋白上调。这些结果表明，卡里翁和 ANP 信号调节骨骼发育和稳态中的软骨细胞分化，表明增强 ANP 信号可能改善骨质疏松症患者的骨质量。
