2026-03-10T12:34:31Z https://mdu.repo.nii.ac.jp/oai

oai:mdu.repo.nii.ac.jp:00003016 2023-06-19T07:49:41Z 170:553

Macrophages promote bone regeneration through the activation of LepR (+) cells マクロファージはLepR陽性細胞を活性化し骨再生を促進する He, Zhifeng 何, 治鋒 open access 2022 甲第249号 application/pdf ABSTRACT Macrophages not only clean up damaged tissues but also promote the proliferation and differentiation of stem cells during the regeneration process in various tissues such as bone and muscle. However,the mechanisms by which macrophages promote bone regeneration has remained to be elucidated.We have shown here that macrophages promote the differentiation of an osteogenic progenitor Leptin Receptor (LepR)(+)lineage cells during the bone regeneration process through Wnt/β‑catenin signals.The cortical bone of tibiae was punctured in LepR‑Cre;Rosa26‑tdTomato(tdTomato)mice and then the clodronate liposome(Clo‑lip)or control liposome(Ctrl‑lip)was intraperitoneally injected into those mice to deplete macrophages.F4/80(+) macrophages was largely depleted in Clo‑lip‑treated mice. Micro CT analysis revealed that the newly formed bone volume in Clo‑lip‑treated mice was significantly lower than that in Ctrl‑lip‑treated mice in the bone injury site at 7 days post injury (dpi).LepR‑Cre labeled bone marrow stromal cells were markedly increased in Ctrl‑lip‑treated but not in Clo‑lip‑treated mice in the bone injury site at 4 dpi and the percentage of proliferating Ki67(+)LepR(+) cells is lower in Clo‑lip‑treated mice.Most of Sp7(+) osteoblasts in the injury site at 4 and 7 dpi were labeled by LepR‑Cre, suggesting that osteoblasts are differentiated from LepR‑Cre‑labeled lineage cells.To clarify the involvement of Wnt signals in the differentiation of LepR(+) cells into osteoblasts,the bone regeneration was examined using tamoxifen‑treated Axin2‑CreERT2;tdTomato mice in which cells with activated Wnt/β‑catenin signals express red fluorescent protein tdTomato. Clo‑lip administration decreased the percentage of Axin2‑ tomato(+) Sp7(+) cells in the bone injury site at 7 dpi.Together, macrophages promote Wnt signals in LepR(+) cells and then facilitate bone regeneration. eng doctoral thesis VoR https://mdu.repo.nii.ac.jp/records/3016 甲第249号 博士（歯学） 2022-09-07 松本歯科大学