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<p>MicroRNAs (miRNAs), including the <i>let-7</i> family, have been shown to regulate osteogenic differentiation of human mesenchymal stem cells. Moreover, <i>let-7</i> miRNAs were upregulated in the muscle tissue of patients who formed ectopic bone compared to patients who did not form ectopic bone after injury. Here we investigated the expression and role of the insulin-like growth factor 2 binding protein genes (<i>IGF2BP1</i>, <i>IGF2BP2</i>, and <i>IGF2BP3</i>), known targets of the <i>let-7</i> miRNAs, during human in vitro osteogenic differentiation. <i>Let-7a</i> and <i>let-7b</i> were slightly upregulated on osteogenic differentiation day 7, downregulated on day 14, and slightly upregulated or unchanged on days 21 and 28. <i>Let-7d</i> and <i>let-7f</i> were upregulated on days 7, 14, 21, and 28. <i>IGF2BP1</i> and <i>IGF2BP2</i> were mildly modulated or unchanged on days 7, 21, and 28, and significantly downregulated on day 14, whereas <i>IGF2BP3</i> was slightly upregulated on day 7 and slightly downregulated on days 14, 21, and 28. Following <i>IGF2BP1</i> knockdown (KD), <i>ALPL</i> was upregulated on days 7 and 14, while <i>RUNX2</i> and <i>BGLAP</i> were mildly upregulated on day 7 and mildly downregulated on day 14. We also observed more calcium deposits on IGF2BP1-KD compared to the control on osteogenic day 14. Finally, downregulation of the <i>IGF2BP2-3</i> genes had no major effects on osteogenic differentiation. Altogether, we characterized the differential expression of members from the <i>let-7</i>-<i>IGF2BP</i> axis during human in vitro osteogenic differentiation and demonstrated a novel mechanistic insight where <i>IGF2BP1</i> may enhance the osteogenic commitment of human bone-marrow mesenchymal stem cells.</p>

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Expression Profile and Role of the IGF2BP1-3 Genes During Human in vitro Osteogenic Differentiation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月9日

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  • Laila Robinson,
  • Hisae Cole,
  • Emma X. Melton,
  • Xinyi Yin,
  • Nica Omandan,
  • Nicole Cubbage,
  • Amy Acosta Cruz,
  • Leah Friedman,
  • Katherine Perez-Nesmith,
  • Morgan Jones,
  • Aldo Omar Pinedo,
  • Sofiya Igorevna Biryukova,
  • Chloe Matz,
  • Lane Bradley,
  • Jillian Lakey,
  • Jaira Ferreira de Vasconcellos

摘要

MicroRNAs (miRNAs), including the let-7 family, have been shown to regulate osteogenic differentiation of human mesenchymal stem cells. Moreover, let-7 miRNAs were upregulated in the muscle tissue of patients who formed ectopic bone compared to patients who did not form ectopic bone after injury. Here we investigated the expression and role of the insulin-like growth factor 2 binding protein genes (IGF2BP1, IGF2BP2, and IGF2BP3), known targets of the let-7 miRNAs, during human in vitro osteogenic differentiation. Let-7a and let-7b were slightly upregulated on osteogenic differentiation day 7, downregulated on day 14, and slightly upregulated or unchanged on days 21 and 28. Let-7d and let-7f were upregulated on days 7, 14, 21, and 28. IGF2BP1 and IGF2BP2 were mildly modulated or unchanged on days 7, 21, and 28, and significantly downregulated on day 14, whereas IGF2BP3 was slightly upregulated on day 7 and slightly downregulated on days 14, 21, and 28. Following IGF2BP1 knockdown (KD), ALPL was upregulated on days 7 and 14, while RUNX2 and BGLAP were mildly upregulated on day 7 and mildly downregulated on day 14. We also observed more calcium deposits on IGF2BP1-KD compared to the control on osteogenic day 14. Finally, downregulation of the IGF2BP2-3 genes had no major effects on osteogenic differentiation. Altogether, we characterized the differential expression of members from the let-7-IGF2BP axis during human in vitro osteogenic differentiation and demonstrated a novel mechanistic insight where IGF2BP1 may enhance the osteogenic commitment of human bone-marrow mesenchymal stem cells.