BMP2-Dependent Gene Regulatory Network Analysis Reveals Klf4 as a Novel Transcription Factor of Osteoblast Differentiation

The BMP signaling pathway is widely regarded as one of the most important pathways in vertebrate skeletal biology, of which BMP2 is a potent inducer, governing the osteoblast differentiation of bone marrow stromal cells. Scientists used RNA-seq, ATAC-seq, and animal models to characterize the BMP2-dependent gene regulatory network governing osteoblast lineage commitment.
[Cell Death & Disease]
Yu, S., Guo, J., Sun, Z., Lin, C., Tao, H., Zhang, Q., Cui, Y., Zuo, H., Lin, Y., Chen, S., Liu, H., & Chen, Z. (2021). BMP2-dependent gene regulatory network analysis reveals Klf4 as a novel transcription factor of osteoblast differentiation. Cell Death & Disease, 12(2), 1–17. https://doi.org/10.1038/s41419-021-03480-7 Cite
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TRPM8 Channel Inhibitor-Encapsulated Hydrogel as a Tunable Surface for Bone Tissue Engineering

Investigators showed that osteoblasts and Bone Marrow-MSC pools expressed TRPM8, a Ca2+-ion channel critical for bone-mineralization. TRPM8 inhibition triggered up-regulation of key osteogenesis factors; and increased mineralization by osteoblasts.
[Scientific Reports]
Acharya, T. K., Kumar, S., Tiwari, N., Ghosh, A., Tiwari, A., Pal, S., Majhi, R. K., Kumar, A., Das, R., Singh, A., Maji, P. K., Chattopadhyay, N., Goswami, L., & Goswami, C. (2021). TRPM8 channel inhibitor-encapsulated hydrogel as a tunable surface for bone tissue engineering. Scientific Reports, 11(1), 3730. https://doi.org/10.1038/s41598-021-81041-w Cite
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Mesenchymal Stem Cell-Derived Interleukin-28 Drives the Selection of Apoptosis Resistant Bone Metastatic Prostate Cancer

Scientists report mesenchymal stem cell-derived interleukin-28 (IL-28) triggered prostate cancer cell apoptosis via IL-28 receptor alpha STAT1 signaling.
[Nature Communications]
McGuire, J. J., Frieling, J. S., Lo, C. H., Li, T., Muhammad, A., Lawrence, H. R., Lawrence, N. J., Cook, L. M., & Lynch, C. C. (2021). Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer. Nature Communications, 12(1), 723. https://doi.org/10.1038/s41467-021-20962-6 Cite
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Trabecular Bone Organoid Model for Studying the Regulation of Localized Bone Remodeling

Investigators describe a tissue-engineered model that reproduces bone tissue complexity and bone remodeling processes with high fidelity and control. An osteoid-inspired biomaterial—demineralized bone paper—directs osteoblasts to deposit structural mineralized bone tissue and subsequently acquire the resting-state bone lining cell phenotype.
[Science Advances]
Park, Y., Cheong, E., Kwak, J.-G., Carpenter, R., Shim, J.-H., & Lee, J. (2021). Trabecular bone organoid model for studying the regulation of localized bone remodeling. Science Advances, 7(4), eabd6495. https://doi.org/10.1126/sciadv.abd6495 Cite
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Energy Metabolism During Osteogenic Differentiation: The Role of Akt

Investigators tested the effect of osteogenic media containing ascorbate and β-glycerol phosphate, or various osteogenic hormones and growth factors on energy metabolism in long bone- and calvarial bone-derived osteoprogenitors.
[Stem Cells and Development]
Smith, C. O., & Eliseev, R. A. (2020). Energy Metabolism During Osteogenic Differentiation: The Role of Akt. Stem Cells and Development. https://doi.org/10.1089/scd.2020.0141 Cite
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Single-Cell Transcriptome Analysis of Uncultured Human Umbilical Cord Mesenchymal Stem Cells

Scientists investigated freshly isolated, uncultured umbilical cord (UC)-MSCs by single-cell RNA sequencing and found two populations of UC-MSCs.
[Stem Cell Research & Therapy]
Zhang, S., Wang, J. Y., Li, B., Yin, F., & Liu, H. (2021). Single-cell transcriptome analysis of uncultured human umbilical cord mesenchymal stem cells. Stem Cell Research & Therapy, 12(1), 25. https://doi.org/10.1186/s13287-020-02055-1 Cite
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ALKBH5 Suppresses Tumor Progression via an m6A-Dependent Epigenetic Silencing of Pre-miR-181b-1/Yap Signaling Axis in Osteosarcoma

The authors explored the potential involvement of ALKBH5 in osteosarcoma and deciphered the underlying cellular/molecular mechanisms. They discovered downregulated levels of demethylase ALKBH5 were correlated with increased m6A methylation in osteosarcoma cells/tissues compared with normal osteoblasts cells/tissues.
[Cell Death & Disease]
Yuan, Y., Yan, G., He, M., Lei, H., Li, L., Wang, Y., He, X., Li, G., Wang, Q., Gao, Y., Qu, Z., Mei, Z., Shen, Z., Pu, J., Wang, A., Zhao, W., Jiang, H., Du, W., & Yang, L. (2021). ALKBH5 suppresses tumor progression via an m 6 A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma. Cell Death & Disease, 12(1), 1–16. https://doi.org/10.1038/s41419-020-03315-x Cite
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Adiponectin Signaling in Bone Homeostasis, with Age and in Disease

The authors explore the current literature on adiponectin in bone, looking in depth at the comparison between human and murine data in health, with age and in disease.
[Bone Research]
Lewis, J. W., Edwards, J. R., Naylor, A. J., & McGettrick, H. M. (2021). Adiponectin signalling in bone homeostasis, with age and in disease. Bone Research, 9(1), 1–11. https://doi.org/10.1038/s41413-020-00122-0 Cite
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Silencing Long Noncoding RNA Colon Cancer-Associated Transcript-1 Upregulates microRNA-34a-5p to Promote Proliferation and Differentiation of Osteoblasts in Osteoporosis

The authors clarified whether lncRNA CCAT1 could regulate osteoblast proliferation and differentiation in ovariectomized rats with osteoporosis.
[Cancer Gene Therapy]
Hu, F., Jiang, C., Bu, G., Fu, Y., & Yu, Y. (2021). Silencing long noncoding RNA colon cancer-associated transcript-1 upregulates microRNA-34a-5p to promote proliferation and differentiation of osteoblasts in osteoporosis. Cancer Gene Therapy, 1–12. https://doi.org/10.1038/s41417-020-00264-7 Cite
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Kindlin-2 Regulates Skeletal Homeostasis by Modulating PTH1R in Mice

Researchers report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralized the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult bone.
[Signal Transduction and Targeted Therapy]
Fu, X., Zhou, B., Yan, Q., Tao, C., Qin, L., Wu, X., Lin, S., Chen, S., Lai, Y., Zou, X., Shao, Z., Wang, M., Chen, D., Jin, W., Song, Y., Cao, H., Zhang, G., & Xiao, G. (2020). Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice. Signal Transduction and Targeted Therapy, 5(1), 1–13. https://doi.org/10.1038/s41392-020-00328-y Cite
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Metabolic Regulation of Skeletal Cell Fate and Function in Physiology and Disease

The authors discuss recent findings on the roles of cellular metabolism in determining skeletal stem cell fate, coordinating osteoblast and chondrocyte function, and organizing stromal support of hematopoiesis.
[Nature Metabolism]
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