Targeting the PTN/PTPRZ1-ROS Pathway to Promote Bone Regeneration
Kai Zhao1,2, Yusi Guo1,2, Ying He1
1Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Abstract:
Background: 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. Methods: 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. Results: 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. Conclusions: This study elucidates the mechanisms by which PTN promotes osteogenesis and verifies this effect in vivo, offering an effective target for osteoporosis treatment.
Insights
Pleiotrophin (PTN) effectively promotes bone formation and fracture healing in osteoporosis by protecting stem cells from oxidative stress. This study identifies PTN as a promising therapeutic target for osteoporosis treatment.
Area of Science:
- Biomedical Science
- Cell Biology
- Orthopedics
Background:
- Osteoporosis presents a significant global health challenge, impacting quality of life and incurring substantial medical costs.
- Identifying effective therapeutic targets for osteoporosis is critical.
- Pleiotrophin (PTN) is implicated in various biological processes, but its specific roles and mechanisms in osteogenesis and osteoporosis remain incompletely understood.
Purpose of the Study:
- To investigate the effects and underlying mechanisms of Pleiotrophin (PTN) on osteogenic functions.
- To evaluate the therapeutic potential of PTN for osteoporosis treatment.
Main Methods:
- Utilized quantitative PCR, immunofluorescence, ALP detection, TUNEL assay, RNA sequencing, and quantitative proteomics.
- Conducted fracture-healing experiments in osteoporotic rat models.
Main Results:
- PTN significantly inhibited apoptosis and enhanced osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs).
- PTN promoted antioxidant functions, reduced reactive oxygen species (ROS), and protected rBMSCs.
- PTN binds to PTPRZ1, inducing PLCG1 phosphorylation and NCOA3 nuclear translocation, regulating downstream antioxidant pathways.
- PTN demonstrated efficacy in promoting fracture healing in osteoporotic animals.
Conclusions:
- PTN plays a crucial role in promoting osteogenesis through antioxidant mechanisms.
- PTN enhances bone formation and fracture healing in vivo.
- PTN represents a potential therapeutic target for osteoporosis treatment.
