Backgroud

Osteoarthritis (OA) is a common disease caused by chondrocyte dysfunction. KLF10 is a member of the Sp1-like transcription factor family that is involved in regulating osteoblasts, but its expression and regulatory mechanism(s) in chondrocytes are unclear. In the present study, we aimed to investigate the regulatory role of KLF10 on the pathological process of OA.

Methods

KLF10 expression in the cartilaginous tissue of patients with osteoarthritis (OA) was evaluated by immunohistochemistry (IHC). Next, we generated an OA mouse model, and the histological changes in cartilage tissue were verified using H&E staining, Safranin O-Fast Green staining, and IHC assays. KLF10 expression in the articular chondrocytes of OA mice was determined by qRT-PCR and Western blotting. To investigate the role of KLF10 in regulating cell proliferation and migration, a KLF10 overexpression plasmid was constructed and transfected into primary mouse chondrocytes. Subsequently, we used RNA sequencing (RNA-seq) to screen differentially expressed genes in chondrocytes with or without KLF10 overexpression. qRT-PCR was used for verification purposes.

Results

We found that KLF10 was upregulated in the cartilaginous tissue of patients with OA as well as in cartilaginous tissue of the OA mouse model. KLF10 overexpression inhibited the proliferation and migration of chondrocytes. Furthermore, RNA sequencing results identified increased expression of Acvr1 and decreased expression of Inhbb in cells overexpressing KLF10. Changes in mRNA expression of Acvr1 and Inhbb were confirmed by qRT-PCR.

Conclusions

KLF10 inhibits chondrocyte proliferation and migration by regulating the expression of Acvr1 and Inhbb in both human and mouse OA. These data suggest that KLF10 may be a potential therapeutic target for the treatment of OA.

中文翻译：

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KLF10 在骨关节炎中上调，并通过上调 Acvr1 和抑制 inhbb 表达来抑制软骨细胞增殖和迁移

背景

骨关节炎（OA）是一种由软骨细胞功能障碍引起的常见疾病。KLF10是 Sp1 样转录因子家族的成员，参与调节成骨细胞，但其在软骨细胞中的表达和调节机制尚不清楚。在本研究中，我们旨在研究KLF10对 OA 病理过程的调节作用。

方法

通过免疫组织化学 (IHC) 评估骨关节炎 (OA) 患者软骨组织中KLF10的表达。接下来，我们生成了一个 OA 小鼠模型，并使用 H&E 染色、番红 O-Fast Green 染色和 IHC 测定验证了软骨组织的组织学变化。通过qRT-PCR和Western印迹测定OA小鼠关节软骨细胞中KLF10的表达。为了研究KLF10在调节细胞增殖和迁移中的作用，构建了一个 KLF10 过表达质粒并转染到原代小鼠软骨细胞中。随后，我们使用 RNA 测序 (RNA-seq) 筛选有或没有KLF10的软骨细胞中的差异表达基因过度表达。qRT-PCR 用于验证目的。

结果

我们发现KLF10在 OA 患者的软骨组织以及 OA 小鼠模型的软骨组织中上调。KLF10过表达抑制软骨细胞的增殖和迁移。此外，RNA 测序结果确定过表达 KLF10 的细胞中Acvr1的表达增加，而Inhbb的表达减少。qRT-PCR 证实了Acvr1和Inhbb的 mRNA 表达变化。

结论

KLF10通过调节人和小鼠 OA中 Acvr1和Inhbb的表达来抑制软骨细胞增殖和迁移。这些数据表明，KLF10可能是治疗 OA 的潜在治疗靶点。