Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.
Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.
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DOI：
10.1038/ncomms10959
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发表时间：
2016-03-24
影响因子：
16.6
通讯作者：
Tsumaki N
中科院分区：
文献类型：
--
作者：
Yahara Y;Takemori H;Okada M;Kosai A;Yamashita A;Kobayashi T;Fujita K;Itoh Y;Nakamura M;Fuchino H;Kawahara N;Fukui N;Watanabe A;Kimura T;Tsumaki N
骨关节炎是一种常见的使人衰弱的关节疾病。骨关节炎的风险因素包括年龄，这与关节软骨变薄有关。在这里，我们产生了软骨细胞特异性盐诱导激酶3（Sik3）条件性敲除小鼠，由于更大的软骨细胞群，这些小鼠对骨关节炎具有抵抗力，关节软骨增厚。我们还鉴定了一种可食用的蕨菜化合物，pterosin B，作为Sik 3途径抑制剂。我们发现Sik3缺失或关节内注射小鼠的蝶呤B抑制软骨细胞肥大，并保护软骨免受骨关节炎。总的来说，我们的研究结果表明Sik 3调节关节软骨的稳态，并且是治疗骨关节炎的靶点，而蝶呤B作为候选治疗剂。 需要治疗来预防软骨细胞肥大和关节软骨变薄，这是骨关节炎关节破坏的特征。在这里，作者表明，干扰Sik3信号传导可以增加软骨细胞群的大小，并降低手术诱导的骨关节炎小鼠模型的严重程度。
Osteoarthritis is a common debilitating joint disorder. Risk factors for osteoarthritis include age, which is associated with thinning of articular cartilage. Here we generate chondrocyte-specific salt-inducible kinase 3 (Sik3) conditional knockout mice that are resistant to osteoarthritis with thickened articular cartilage owing to a larger chondrocyte population. We also identify an edible Pteridium aquilinum compound, pterosin B, as a Sik3 pathway inhibitor. We show that either Sik3 deletion or intraarticular injection of mice with pterosin B inhibits chondrocyte hypertrophy and protects cartilage from osteoarthritis. Collectively, our results suggest Sik3 regulates the homeostasis of articular cartilage and is a target for the treatment of osteoarthritis, with pterosin B as a candidate therapeutic. Therapies are needed for the prevention of chondrocyte hypertrophy and thinning of articular cartilage, features of osteoarthritic joint destruction. Here, the authors show that interfering with Sik3 signalling can increase the size of the chondrocyte population and reduce severity of a surgically induced mouse model of osteoarthritis.