发表刊物：Advanced Science（2024 IF=14.3/Q1）
AAH-PRTK-1（检测71个人受体酪氨酸激酶磷酸化位点，检测样本：人骨髓间充质干细胞裂解液）
AAH-BMA-2（检测10个人骨代谢相关细胞因子，检测样本：人骨髓间充质干细胞裂解液）
AAH-TGFB-1（检测8个TGFb通路相关氨基酸磷酸化位点，检测样本：人骨髓间充质干细胞裂解液）
DOI：10.1002/advs.202308698
研究摘要
骨质疏松症是一种常见的全身性慢性代谢性骨病，其特征是骨结构和组成的逐渐退化，导致骨密度降低和骨折风险增加。
现有的骨质疏松治疗手段（如激素替代疗法、双膦酸盐、狄诺塞麦等）均存在局限性，例如增加癌症或心血管疾病风险。因此，开发新的预防和治疗策略迫在眉睫。
本研究探讨了Pool 7 Compound 3（P7C3）是否能够减少卵巢切除术（OVX）诱导的骨质疏松症后的进行性骨量丢失和脆弱性。结果证实，OVX会导致骨量减少和骨质疏松，同时显著增加脂肪生成性体重。P7C3治疗显著降低了破骨细胞活性、骨髓脂肪化、全身体重增加，并保留了骨面积、骨结构和机械强度。
利用多种精准蛋白质组学芯片检测分析显示，血小板衍生生长因子-BB（PDGF-BB）和白血病抑制因子（LIF）显著上调，而白细胞介素-1 R6（IL-1 R6）和核因子κB受体激活剂（RANK）下调。这些数据表明，P7C3通过转化生长因子-β/SMAD和Wnt/β-连环蛋白信号通路靶向了炎症、骨代谢和脂肪代谢的关键调控因子。
研究结果分析
1. P7C3促进hBMSC的成骨分化并抑制脂肪生成
2. P7C3激活多种受体酪氨酸激酶
3. P7C3体外抑制破骨细胞成熟和破骨细胞活性
4. 在ovx诱导的骨质疏松动物模型中，P7C3体内无毒，可减少破骨细胞活性和骨质流失，同时保持生物力学强度
在OVX大鼠中，P7C3治疗显著提高了骨的断裂应力、屈服应力和极限应力，并保持了骨小梁的微结构。此外，P7C3减少了骨髓脂肪化和内脏脂肪的积累。
大鼠血清细胞多因子检测（QAR-CAA-282）分析显示，P7C3上调了PDGF-BB、LIF等促骨形成因子，同时下调了IL-1 R6和RANK等促炎因子（图B-C）。肠道微生物群分析表明，P7C3增加了抗炎细菌（如Porphyromonadaceae bacterium）的丰度。
讨论与总结
本研究通过骨代谢、RTK磷酸化、人类及大鼠蛋白质组学多种蛋白质组学芯片，首次全方位证明P7C3通过下调RANK表达、调节TGF-β/SMAD和Wnt/β-catenin信号通路，以及改变肠道微生物群组成，有效对抗OVX诱导的骨丢失和脆性。P7C3不仅抑制破骨细胞活性和脂肪生成，还促进成骨分化，维持骨强度和结构。这些发现为开发新型多功能骨质疏松治疗策略提供了重要依据。
P7C3的广谱作用（包括神经保护、抗炎和代谢调节）使其成为治疗年龄相关疾病（如骨质疏松症）的潜在候选药物。未来的研究应进一步探索P7C3在临床中的应用潜力及其作用机制的细节
文章信息：F Wei，M Hughes，M Omer，C Ngo，AS Pugazhendhi，E Kolanthai，M Aceto，Y Ghattas，M Razavi，TJ Kean. A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovarlectomized Rat Model of Postmenopausal Osteoporosis. Advanced Science (2024) DOI：10.1002/advs.202308698
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