Sardar Anirban, Verma Shikha, Raj Anuj, Maji Bhaskar, Trivedi Ritu
Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India.
J Bone Metab. 2025 May;32(2):69-82. doi: 10.11005/jbm.25.841. Epub 2025 May 31.
The bone marrow niche comprises diverse cellular populations, including multipotent bone marrow-derived stem cells (BMSCs). Understanding the biology underlying the differentiation of BMSCs into osteogenic and adipogenic commitment in preserving bone health is key due to their inverse correlation. Biological processes such as cellular migration also serve as a crucial player during this differentiation and eventually contribute to various skeletal pathologies such as fractures, osteoporosis, and osteoarthritis. This is also crucial in developing various regenerative therapies involving BMSCs.
To explore the differential migration of BMSCs, cells were initially directed into osteogenic or adipogenic commitment as confirmed by the mineralized matrix and lipid droplet formation for osteogenic and adipogenic commitment, respectively. The differential level of cellular migration was then assessed using the scratch wound healing assay, cell adhesion assay, and transwell migration assay.
The cellular differentiation was confirmed by the differential expression patterns of key markers, as determined by quantitative real-time reverse transcription-polymerase chain reaction and immunoblotting study. Moreover, the migration data indicates that BMSCs undergoing osteogenic commitment tend to migrate more compared to adipogenic cells, which is possibly attributed to the differential expression of integrins such as Itgα1, and Itgα5. The putative role of the Sdf1/Cxcr4 axis in this account was further established by utilizing a selective inhibitor of Cxcr4.
This study sheds light on the differential migratory property of the BMSCs directed towards a specific lineage. It also highlights the need for a comprehensive understanding of the intricate biological interplay governing this peculiar cellular behaviour.
骨髓生态位由多种细胞群体组成，包括多能骨髓来源干细胞（BMSCs）。由于骨髓间充质干细胞向成骨和成脂分化与骨骼健康的维持呈负相关，了解其分化背后的生物学机制对于维持骨骼健康至关重要。细胞迁移等生物学过程在这种分化过程中也起着关键作用，并最终导致各种骨骼疾病，如骨折、骨质疏松症和骨关节炎。这对于开发涉及骨髓间充质干细胞的各种再生疗法也至关重要。
为了探究骨髓间充质干细胞的差异迁移，首先将细胞诱导成骨或成脂分化，分别通过矿化基质和成脂分化的脂滴形成来确认。然后使用划痕伤口愈合试验、细胞黏附试验和Transwell迁移试验评估细胞迁移的差异水平。
通过定量实时逆转录-聚合酶链反应和免疫印迹研究确定的关键标志物的差异表达模式证实了细胞分化。此外，迁移数据表明，与成脂细胞相比，经历成骨分化的骨髓间充质干细胞倾向于更多地迁移，这可能归因于整合素如Itgα1和Itgα5的差异表达。通过使用Cxcr4的选择性抑制剂进一步确定了Sdf1/Cxcr4轴在此过程中的假定作用。
本研究揭示了骨髓间充质干细胞向特定谱系分化的差异迁移特性。它还强调了全面了解控制这种特殊细胞行为的复杂生物相互作用的必要性。
