Zhao Kai, Guo Yusi, He Ying, Wu Yujia, Hu Zhewen, Chi Xiaopei, Deng Xuliang
Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China.
NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Laboratory of Biomedical Materials, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Biomedicines. 2025 Mar 12;13(3):695. doi: 10.3390/biomedicines13030695.
: Osteoporosis is a global health problem that significantly decreases patients' quality of life and causes tremendous medical burdens. Therefore, exploring effective targeting strategies for osteoporosis treatment is crucial. Previous studies have indicated that pleiotrophin (PTN) was a secretory factor involved in several biological processes, such as angiogenesis, neural development, and abnormal osteogenic functions in osteoporosis. However, the roles of PTN in osteogenics and the mechanisms remain unclear. : In this study, we explored the effects and mechanisms of PTN in regulating osteogenic functions using real-time quantitative PCR, immunofluorescence, ALP detection, a TUNEL assay, RNA sequencing, and phosphorylation quantitative proteomics. Fracture-healing experiments in osteoporosis rats were also conducted to evaluate the osteogenic functions of PTN in vivo. : We found that PTN significantly inhibited apoptosis and promoted the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs). Further experiments showed that PTN regulated the biological functions of rBMSCs by promoting antioxidant functions and reducing cellular reactive oxygen species (ROS), thereby protecting rBMSCs from accumulated ROS. Additionally, we found that PTN binds to the PTPRZ1 receptor, inducing intracellular PLCG1 phosphorylation and NCOA3 nuclear translocation, which regulate the downstream antioxidant functions of rBMSCs. Additionally, we verified that PTN effectively promoted fracture healing in osteoporotic animals. : This study elucidates the mechanisms by which PTN promotes osteogenesis and verifies this effect in vivo, offering an effective target for osteoporosis treatment.
骨质疏松症是一个全球性的健康问题，它会显著降低患者的生活质量并造成巨大的医疗负担。因此，探索有效的骨质疏松症治疗靶向策略至关重要。先前的研究表明，多效生长因子（PTN）是一种分泌因子，参与多种生物学过程，如血管生成、神经发育以及骨质疏松症中的异常成骨功能。然而，PTN在成骨过程中的作用及其机制仍不清楚。
在本研究中，我们使用实时定量PCR、免疫荧光、碱性磷酸酶检测、TUNEL检测、RNA测序和磷酸化定量蛋白质组学，探索了PTN在调节成骨功能方面的作用和机制。还进行了骨质疏松症大鼠的骨折愈合实验，以评估PTN在体内的成骨功能。
我们发现PTN显著抑制大鼠骨髓间充质干细胞（rBMSCs）的凋亡并促进其成骨分化。进一步的实验表明，PTN通过促进抗氧化功能和减少细胞内活性氧（ROS）来调节rBMSCs的生物学功能，从而保护rBMSCs免受ROS积累的影响。此外，我们发现PTN与PTPRZ1受体结合，诱导细胞内PLCG1磷酸化和NCOA3核转位，从而调节rBMSCs的下游抗氧化功能。此外，我们验证了PTN能有效促进骨质疏松症动物的骨折愈合。
本研究阐明了PTN促进成骨的机制，并在体内验证了这种作用，为骨质疏松症治疗提供了一个有效的靶点。
