β‐Catenin signaling is important for osteogenesis and hematopoiesis recovery following methotrexate chemotherapy in rats,Journal of Cellular Physiology

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β‐Catenin signaling is important for osteogenesis and hematopoiesis recovery following methotrexate chemotherapy in rats
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-10-20 , DOI: 10.1002/jcp.30114
Jian Fan ₁ , Yu-Wen Su ₂ , Mohammadhossein Hassanshahi ₂ , Chia-Ming Fan ₂ , Yaser Peymanfar ₂ , Alessandro Piergentili ₃ , Fabio Del Bello ₃ , Wilma Quaglia ₃ , Cory J Xian _{1,

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Affiliation

Cancer chemotherapy can significantly impair the bone formation and cause myelosuppression; however, their recovery potentials and mechanisms remain unclear. This study investigated the roles of the β‐catenin signaling pathway in bone and bone marrow recovery potentials in rats treated with antimetabolite methotrexate (MTX) (five once‐daily injections, 0.75 mg/kg) with/without β‐catenin inhibitor indocyanine green (ICG)‐001 (oral, 200 mg/kg/day). ICG alone reduced trabecular bone volume and bone marrow cellularity. In MTX‐treated rats, ICG suppressed bone volume recovery on Day 11 after the first MTX injection. ICG exacerbated MTX‐induced decreases on Day 9 osteoblast numbers on bone surfaces, their formation in vitro from bone marrow stromal cells (osteogenic differentiation/mineralization), as well as expression of osteogenesis‐related markers Runx2, Osx, and OCN in bone, and it suppressed their subsequent recoveries on Day 11. On the other hand, ICG did not affect MTX‐induced increased osteoclast density and the level of the osteoclastogenic signal (RANKL/OPG expression ratio) in bone, suggesting that ICG inhibition of β‐catenin does nothing to abate the increased bone resorption induced by MTX. ICG also attenuated bone marrow cellularity recovery on Day 11, which was associated with the suppressed recovery of CD34⁺ or c‐Kit⁺hematopoietic progenitor cell contents. Thus, β‐catenin signaling is important for osteogenesis and hematopoiesis recoveries following MTX chemotherapy.

中文翻译：

β-连环蛋白信号对大鼠甲氨蝶呤化疗后的成骨和造血恢复很重要

癌症化疗可显着损害骨形成并引起骨髓抑制；然而，它们的恢复潜力和机制仍不清楚。本研究调查了 β-连环蛋白信号通路在用抗代谢物甲氨蝶呤 (MTX)（每天注射 5 次，0.75 mg/kg）和/不加/不加 β-连环蛋白抑制剂吲哚菁绿治疗的大鼠骨和骨髓恢复潜能中的作用。 ICG)-001（口服，200 毫克/公斤/天）。ICG 单独减少小梁骨量和骨髓细胞组成。在 MTX 治疗的大鼠中，ICG 抑制了第一次 MTX 注射后第 11 天的骨量恢复。在第 9 天，ICG 加剧了 MTX 诱导的骨表面成骨细胞数量减少，它们在体外从骨髓基质细胞形成（成骨分化/矿化），以及骨中成骨相关标志物 Runx2、Osx 和 OCN 的表达，并在第 11 天抑制了它们随后的恢复。另一方面，ICG 不影响 MTX 诱导的破骨细胞密度增加和破骨细胞生成信号水平（RANKL/OPG 表达比）在骨中，表明 ICG 对 β-catenin 的抑制对减轻 MTX 诱导的骨吸收增加没有作用。ICG 还在第 11 天减弱了骨髓细胞数量的恢复，这与 CD34 的恢复受到抑制有关表明 ICG 对 β-catenin 的抑制对减轻 MTX 诱导的骨吸收增加没有任何作用。ICG 还在第 11 天减弱了骨髓细胞数量的恢复，这与 CD34 的恢复受到抑制有关表明 ICG 对 β-catenin 的抑制对减轻 MTX 诱导的骨吸收增加没有任何作用。ICG 还在第 11 天减弱了骨髓细胞数量的恢复，这与 CD34 的恢复受到抑制有关⁺或 c-Kit ⁺造血祖细胞含量。因此，β-连环蛋白信号传导对于 MTX 化疗后的成骨和造血恢复很重要。

更新日期：2020-10-20

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