Discipline of Physiology, University of Adelaide, Adelaide 5005, Australia.
Curr Mol Med. 2010 Jul;10(5):440-53. doi: 10.2174/156652410791608243.
The bone marrow microenvironment houses haematopoietic stem cells (HSC), mesenchymal stem cells (MSC) and their progeny, supports haematopoiesis, osteogenesis, osteoclastogenesis, and adipogenesis. It plays a key role in maintaining homeostatic production of erythroid, myeloid or lymphoid cells, appropriate bone mass and bone health throughout life. Through cell-cell adhesion and chemotactic axes, a reciprocal inter-dependent relationship exists between these two cell lineages. Following chemotherapy-induced myelosuppression observed in cancer patients, HSCs are induced to enter into the cell cycle in order to re-establish the damaged microenvironment. These cells not only have the capacity to mobilize to the peripheral blood, but the ability to repopulate the marrow cavity as required. However, depending on the dosage and length of chemotherapy treatment, complications in bone and bone marrow recovery occur. This may manifest as marrow haematopoietic depletion, high marrow fat content, reduced bone formation and aggravated osteoclastic bone resorption. Although the molecular and cellular mechanisms governing injured states of the marrow microenvironment are yet to be fully elucidated, many reports have demonstrated the CXCL12/CXCR4 axis plays an important role in regulating the two cell lineages. Their interaction maintains bone marrow homeostasis and orchestrates its regeneration following chemotherapy. This review explores movement of MSC and HSC, haematopoiesis, commitment of osteoblasts, osteoclasts, and adipocytes, as well as the major signalling pathways that regulate these cellular processes under chemotherapy-treated conditions. This review also discusses molecular targets that are being used clinically or are currently under investigation for preserving the bone marrow microenvironment during or enhancing recovery after chemotherapy.
骨髓微环境中存在造血干细胞（HSC）、间充质干细胞（MSC）及其后代，支持造血、成骨、破骨和成脂。它在维持红细胞、髓样细胞或淋巴样细胞的稳态产生、适当的骨量和骨骼健康方面发挥着关键作用。通过细胞-细胞黏附和趋化轴，这两种细胞谱系之间存在着相互依存的关系。在癌症患者中观察到化疗引起的骨髓抑制后，HSC 被诱导进入细胞周期，以重建受损的微环境。这些细胞不仅有动员到外周血的能力，而且有按需重新填充骨髓腔的能力。然而，取决于化疗的剂量和持续时间，会出现骨骼和骨髓恢复的并发症。这可能表现为骨髓造血耗竭、骨髓脂肪含量高、骨形成减少和破骨细胞骨吸收加剧。尽管调控骨髓微环境受损状态的分子和细胞机制尚未完全阐明，但许多报告表明，CXCL12/CXCR4 轴在调节这两种细胞谱系方面发挥着重要作用。它们的相互作用维持着骨髓的稳态，并在化疗后协调其再生。本综述探讨了 MSC 和 HSC 的迁移、造血、成骨细胞、破骨细胞和脂肪细胞的分化，以及在化疗处理条件下调控这些细胞过程的主要信号通路。本综述还讨论了目前临床上正在使用或正在研究中的分子靶点，以在化疗期间或增强化疗后的恢复过程中保护骨髓微环境。
