Graduate School of Biotechnology and Department of Genetic Engineering, College of Life Science, Kyung Hee University, Seochun-dong, Kiheung-ku, Yong In, Republic of Korea.
Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, Republic of Korea.
Aging (Albany NY). 2020 Oct 27;12(20):20753-20777. doi: 10.18632/aging.104008.
Osteoporosis is an age-related disease caused by imbalanced bone remodeling resulting from excessive bone resorption. Osteoporosis is tightly linked with induction of chronic inflammation, which activates osteoclasts and impairs osteoprogenitor in bone marrow. T helper 17 (Th17) cells have been recently recognized as one of major inducers in the pathophysiology of bone loss by secreting IL-17. Thus, modulation of Th17 development is anticipated to affect the progression of osteoporosis. Substance P (SP) is reported to provide anti-inflammatory effects by controlling immune cell profile and also, promote restoration of damaged stem cell niches-the bone marrow-by repopulating BMSCs or potentiating its paracrine ability. This study aimed to explore the therapeutic effects of systemically injected SP on ovariectomy (OVX)-induced osteoporosis. Resultantly, SP injection obviously blocked OVX-induced impairment of bone microarchitecture and reduction of the mineral density. In osteoporotic condition, SP could ameliorate chronic inflammation by promoting Treg cell polarization and inhibiting the development of osteoclastogenic Th17 cells. Moreover, SP could rejuvenate stem cell and enable stem cells to repopulate and differentiate into osteoblast. Collectively, our study strongly suggests that SP treatment can block osteoporosis and furthermore, SP treatment provides therapeutic effect on chronic disease with inflammation and stem cell dysfunction.
骨质疏松症是一种与年龄相关的疾病，由骨吸收过度导致的骨重建失衡引起。骨质疏松症与慢性炎症的诱导密切相关，慢性炎症激活破骨细胞并损害骨髓中的成骨前体细胞。辅助性 T 细胞 17（Th17）细胞最近被认为是骨丢失病理生理学中的主要诱导因子之一，通过分泌 IL-17。因此，调节 Th17 的发育有望影响骨质疏松症的进展。神经肽 P（SP）通过控制免疫细胞的特征，也被报道具有抗炎作用，并且通过重新填充 BMSCs 或增强其旁分泌能力，促进受损干细胞龛（骨髓）的恢复。本研究旨在探讨系统注射 SP 对卵巢切除（OVX）诱导的骨质疏松症的治疗作用。结果表明，SP 注射明显阻断了 OVX 诱导的骨微结构损伤和矿物质密度降低。在骨质疏松症的情况下，SP 可以通过促进 Treg 细胞极化和抑制破骨细胞生成性 Th17 细胞的发育来改善慢性炎症。此外，SP 可以使干细胞恢复活力，并使干细胞重新填充和分化为成骨细胞。总之，我们的研究强烈表明，SP 治疗可以阻断骨质疏松症，此外，SP 治疗对具有炎症和干细胞功能障碍的慢性疾病具有治疗作用。
