PDF(Pubmed)
Abstract：
The existing suite of therapies for bone diseases largely act to prevent further bone loss but fail to stimulate healthy bone formation and repair. We describe an endogenous osteopeptide (PEPITEM) with anabolic osteogenic activity, regulating bone remodeling in health and disease. PEPITEM acts directly on osteoblasts through NCAM-1 signaling to promote their maturation and formation of new bone, leading to enhanced trabecular bone growth and strength. Simultaneously, PEPITEM stimulates an inhibitory paracrine loop: promoting osteoblast release of the decoy receptor osteoprotegerin, which sequesters RANKL, thereby limiting osteoclast activity and bone resorption. In disease models, PEPITEM therapy halts osteoporosis-induced bone loss and arthritis-induced bone damage in mice and stimulates new bone formation in osteoblasts derived from patient samples. Thus, PEPITEM offers an alternative therapeutic option in the management of diseases with excessive bone loss, promoting an endogenous anabolic pathway to induce bone remodeling and redress the imbalance in bone turnover.
摘要：
现有的骨疾病疗法主要用于防止进一步的骨丢失,但不能刺激健康的骨形成和修复。我们描述了一种具有合成代谢成骨活性的内源性骨肽（PEPITEM），在健康和疾病中调节骨骼重塑。PEPITEM通过NCAM-1信号直接作用于成骨细胞，促进其成熟和新骨的形成，导致增强骨小梁生长和强度。同时,PEPITEM刺激抑制性旁分泌环：促进诱骗受体骨保护素的成骨细胞释放，隔离了RANKL，从而限制破骨细胞活性和骨吸收。在疾病模型中,PEPITEM治疗可阻止骨质疏松症诱导的小鼠骨丢失和关节炎诱导的骨损伤，并刺激患者样品中成骨细胞的新骨形成。因此，PEPITEM在治疗骨质流失过多的疾病方面提供了一种替代治疗选择，促进内源性合成代谢途径以诱导骨重建并纠正骨转换的失衡。
