Wang Jun, Zhao Changyu, Zhao Wenpeng, Li Songnan
School of Tourism and Cuisine, Yangzhou University, Yangzhou 225127, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou 225009, China.
Heliyon. 2024 Jul 2;10(13):e34027. doi: 10.1016/j.heliyon.2024.e34027. eCollection 2024 Jul 15.
Osteoporosis is a common diabetic consequence that negatively affects patients' health and quality of life. Nevertheless, there is mutual interference between clinical drugs intended to regulate blood glucose and bone metabolism. Therefore, it is crucial to look for new treatment targets that effectively control blood glucose and safely protect the bone health of patients with diabetes. In this study, mice given a high-fat diet were shown to be resistant to osteoporosis and diabetes when protein phosphatase 5 (PP5) knockout (KO) mice were used. Serum markers of bone remodeling show that PP5 KO mice are resistant to decreased bone formation and increased bone resorption brought on by diabetes. The absence of PP5 resists the reduction of osteoblast differentiation and the enhancement of osteoclast differentiation in diabetic mice, according to the in vitro osteoblast differentiation of bone mesenchymal stem cells and osteoclast differentiation of bone marrow-derived macrophages. Subsequent investigation revealed that PP5 deficiency increases the expression of the key regulator of osteoblast differentiation, runt-related transcription factor 2, and decreases the activity of the receptor activator of the nuclear factor-κB ligand/osteoprotegerin pathway, a crucial regulatory signaling pathway for osteoclast differentiation. In conclusion, we discovered that PP5 deficiency protects diabetic mice against osteoporosis for the first time.
骨质疏松症是一种常见的糖尿病并发症，会对患者的健康和生活质量产生负面影响。然而，用于调节血糖和骨代谢的临床药物之间存在相互干扰。因此，寻找能够有效控制血糖并安全保护糖尿病患者骨骼健康的新治疗靶点至关重要。在本研究中，当使用蛋白磷酸酶5（PP5）基因敲除（KO）小鼠时，给予高脂饮食的小鼠显示出对骨质疏松症和糖尿病具有抗性。骨重塑的血清标志物表明，PP5基因敲除小鼠对糖尿病引起的骨形成减少和骨吸收增加具有抗性。根据骨髓间充质干细胞的体外成骨细胞分化和骨髓来源巨噬细胞的破骨细胞分化，PP5的缺失可抵抗糖尿病小鼠中成骨细胞分化的减少和破骨细胞分化的增强。随后的研究表明，PP5缺乏会增加成骨细胞分化关键调节因子—— runt相关转录因子2的表达，并降低核因子κB配体/骨保护素途径（破骨细胞分化的关键调节信号通路）的活性。总之，我们首次发现PP5缺乏可保护糖尿病小鼠免受骨质疏松症的影响。
