Maeda Ayako, Kikuiri Takashi, Yoshimura Yoshitaka, Yawaka Yasutaka, Shirakawa Tetsuo
Department of Dentistry for Children and Disabled Individuals, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido 060-8586, Japan.
Department of Pediatric Dentistry, Nihon University School of Dentistry, Tokyo 101-8310, Japan.
Exp Ther Med. 2022 Apr;23(4):299. doi: 10.3892/etm.2022.11228. Epub 2022 Feb 21.
Stem cells from human exfoliated deciduous teeth (SHED) are mesenchymal stem cells with multipotent differentiation potential present in the dental pulp tissue of the deciduous teeth. SHED produce secretions that have immunomodulatory and regenerative functions. In the present study, we investigated the effects of SHED-conditioned medium (SHED-CM) on osteopenia induced by the ovariectomy (OVX) phenotype and its corresponding immunological changes. Eleven-week-old female C3H/HeJ mice were subjected to OVX. SHED-CM was administered intraperitoneally in these mice for 4 weeks starting immediately after OVX. SHED-CM improved bone mass after OVX and elevated the polarization of M2 macrophages in the peritoneal cavity. SHED-CM also suppressed an OVX-induced increase in interferon-γ (INF-γ) and interleukin-17 (IL-17) concentrations in the peripheral blood. Inhibition of M2 macrophage polarization with neutralizing antibodies did not reduce the concentration of IFN-γ and IL-17 in peripheral blood, which were increased by OVX, and did not alleviate osteopenia induced by the OVX phenotype. Mechanistically, these findings suggest that SHED-CM alleviates bone resorption by suppressing the activation of IFN-γ and IL-17 cells by polarizing M2 macrophages. In conclusion, our data indicate that SHED-CM contains active secretions that may have promising efficacy to ameliorate OVX-induced osteopenia. We suggest that SHED-CM has the potential to be used as a novel therapeutic agent to inhibit osteoporosis.
人脱落乳牙干细胞(SHED)是存在于乳牙牙髓组织中的具有多能分化潜能的间充质干细胞。SHED产生具有免疫调节和再生功能的分泌物。在本研究中,我们研究了SHED条件培养基(SHED-CM)对去卵巢(OVX)表型诱导的骨质减少及其相应免疫变化的影响。11周龄雌性C3H/HeJ小鼠接受去卵巢手术。在去卵巢后立即开始对这些小鼠腹腔注射SHED-CM,持续4周。SHED-CM改善了去卵巢后的骨量,并提高了腹腔中M2巨噬细胞极化。SHED-CM还抑制了去卵巢诱导的外周血中干扰素-γ(INF-γ)和白细胞介素-17(IL-17)浓度的增加。用中和抗体抑制M2巨噬细胞极化并没有降低去卵巢后外周血中增加的INF-γ和IL-17的浓度,也没有减轻去卵巢表型诱导的骨质减少。从机制上讲,这些发现表明SHED-CM通过极化M2巨噬细胞抑制IFN-γ和IL-17细胞的激活来减轻骨吸收。总之,我们的数据表明SHED-CM含有活性分泌物,可能对改善去卵巢诱导的骨质减少具有有前景的疗效。我们认为SHED-CM有潜力用作抑制骨质疏松症的新型治疗剂。