Yang Kunkun, Zhu Yuan, Shao Yuzi, Jiang Yuhe, Zhu Lei, Liu Yaoshan, Zhang Ping, Liu Yunsong, Zhang Xiao, Zhou Yongsheng
Department of Prosthodontics, Peking University School and Hospital of Stomatology, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
National Center of Stomatology, National Clinical Research Center for Oral Disease, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, NHC Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
Biomedicines. 2024 Mar 25;12(4):730. doi: 10.3390/biomedicines12040730.
Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.
骨质疏松症是一种常见的退行性骨病。鉴于人口老龄化加剧，骨质疏松症的治疗仍然是一项临床挑战。人牙髓干细胞（DPSCs）是一种间充质干细胞（MSCs），易于获取且具有高增殖能力，在骨质疏松症的治疗中发挥着重要作用。然而，MSCs在体内使用时会在短时间内发生凋亡；因此，凋亡小泡（apoVs）受到了越来越多的关注。目前，DPSC来源的apoVs的成骨作用尚不清楚；因此，本研究旨在确定DPSC来源的apoVs在骨再生中的作用及其潜在机制。我们发现MSCs可以摄取DPSC来源的apoVs，进而在体外促进MSCs的成骨作用。此外，apoVs可以增加小鼠骨质疏松模型中的骨小梁数量和骨矿物质密度，并可以在体内促进大鼠颅骨缺损处的骨形成。机制上，apoVs通过激活细胞外调节激酶（ERK）1/2信号通路促进MSCs的成骨作用。因此，我们提出了一种包含DPSC来源的apoVs的新型疗法，这是一种治疗骨质流失和骨缺损的有前景的方法。
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