Yan Song, Zeng Jiancong, Dong Wei, Wei Jinsong
The First Clinical Medical College of Guangdong Medical University, Zhanjiang, China.
Department of Orthopedics, Shiyan People's Hospital, Bao'an District, Shenzhen, China.
J Musculoskelet Neuronal Interact. 2025 Sep 1;25(3):341-350. doi: 10.22540/JMNI-25-341.
To explore the role of cathepsin D (CTSD), a lysosomal aspartyl protease, as a potential biomarker and therapeutic target in the context of osteoporosis.
Utilizing single-cell sequencing data from the Gene Expression Omnibus (GEO) database, we identified differential expression patterns of CTSD in human femoral head tissues between osteoporotic and non-osteoporotic states. Human mesenchymal stem cells (MSCs) were treated with recombinant human CTSD and/or osteogenic induction medium and the role of CTSD on osteoblast differentiation were investigated by RT-qPCR, western blot, immunofluorescence staining and alizarin red staining. The role of CTSD on osteoporotic changes was further verified in ovariectomized mice.
analyses of human mesenchymal stem cells (MSCs) treated with recombinant human CTSD (rhCTSD) under osteogenic induction conditions revealed modulation of osteogenic marker expression, including ALP, COL1A1, and RUNX2. Histological assessments using Alizarin Red staining and immunofluorescence corroborated these findings, demonstrating that CTSD influences osteoblast differentiation and matrix mineralization. studies in mice further supported the role of CTSD, showing that perturbations in this enzyme result in alterations in bone mineral density and volume characteristic of osteoporotic changes.
Collectively, these findings implicate CTSD as a regulator of bone homeostasis and support its potential as a novel target for therapeutic intervention in osteoporosis.
探讨溶酶体天冬氨酸蛋白酶组织蛋白酶D（CTSD）在骨质疏松症中作为潜在生物标志物和治疗靶点的作用。
利用基因表达综合数据库（GEO）中的单细胞测序数据，我们确定了CTSD在骨质疏松和非骨质疏松状态下人类股骨头组织中的差异表达模式。用人重组CTSD和/或成骨诱导培养基处理人间充质干细胞（MSCs），并通过RT-qPCR、蛋白质免疫印迹、免疫荧光染色和茜素红染色研究CTSD对成骨细胞分化的作用。在去卵巢小鼠中进一步验证CTSD对骨质疏松变化的作用。
对在成骨诱导条件下用人重组CTSD（rhCTSD）处理的人间充质干细胞（MSCs）的分析显示，成骨标志物表达受到调节，包括碱性磷酸酶（ALP）、I型胶原（COL1A1）和 Runt相关转录因子2（RUNX2）。使用茜素红染色和免疫荧光的组织学评估证实了这些发现，表明CTSD影响成骨细胞分化和基质矿化。在小鼠中的研究进一步支持了CTSD的作用，表明该酶紊乱会导致骨质疏松变化所特有的骨矿物质密度和体积改变。
总的来说，这些发现表明CTSD是骨稳态的调节因子，并支持其作为骨质疏松症治疗干预新靶点的潜力。
