Hu Zhao Ph.D.

Xue, F., Zhao, H., Yuan, Q. and Zhang, S.W. (2021). “[Advances in application of tissue clearing technique in hard tissues].” Zhonghua Kou Qiang Yi Xue Za Zhi 56(6): 598-603.

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Tissue clearing is a novel technique developed within recent years, which could make the tissue optical transparency using physical or chemical methods by refractive index matching. Combined with fluorescence imaging and three-dimensional reconstruction technology, it could achieve three-dimensional observing and analyze the tissue structure at the cellular resolution. The tissue clearing technique is mainly applied to soft tissues, as less to hard tissues. In recent years, many researchers have modified tissue clearing methods and made them suitable for hard tissues, such as bone and teeth. The present paper reviews the recent application of tissue clearing techniques in hard tissues.

Yi, Y., Stenberg, W., Luo, W., Feng, J.Q. and Zhao, H. (2021). “Alveolar Bone Marrow Gli1+ Stem Cells Support Implant Osseointegration.” J Dent Res: 220345211013722.

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Osseointegration is the key issue for implant success. The in vivo properties of cell populations driving the osseointegration process have remained largely unknown. In the current study, using tissue clearing-based 3-dimensional imaging and transgenic mouse model-based lineage tracing methods, we identified Gli1+ cells within alveolar bone marrow and their progeny as the cell population participating in extraction socket healing and implant osseointegration. These Gli1(+) cells are surrounding blood vessels and do not express lineage differentiation markers. After tooth extraction and delayed placement of a dental implant, Gli1(+) cells were activated into proliferation, and their descendants contributed significantly to new bone formation. Ablation of Gli1(+) cells severely compromised the healing and osseointegration processes. Blockage of canonical Wnt signaling resulted in impaired recruitment of Gli1(+) cells and compromised bone healing surrounding implants. Collectively, these findings demonstrate that Gli1(+) cells surrounding alveolar bone marrow vasculature are stem cells supporting dental implant osseointegration. Canonical Wnt signal plays critical roles in regulating Gli1(+) stem cells.

Zhu, Q., Shao, Y., Wang, Z., Chen, X., Li, C., Liang, Z., Jia, M., Guo, Q., Zhao, H., Kong, L. and Zhang, L. (2021). “DeepS: A web server for image optical sectioning and super resolution microscopy based on a deep learning framework.” Bioinformatics Mar 2;btab144. [Epub ahead of print].

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MOTIVATION: Microscopy technology plays important roles in many biological research fields. Solvent-cleared brain high-resolution (HR) 3 D image reconstruction is an important microscopy application. However, 3 D microscopy image generation is time-consuming and expensive. Therefore, we have developed a deep learning framework (DeepS) for both image optical sectioning and super resolution microscopy. RESULTS: Using DeepS to perform super resolution solvent-cleared mouse brain microscopy 3 D image yields improved performance in comparison with the standard image processing workflow. We have also developed a web server to allow online usage of DeepS. Users can train their own models with only one pair of training images using the transfer learning function of the web server. AVAILABILITY: http://deeps.cibr.ac.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Wang, L., Yang, H., Huang, J., Pei, S., Wang, L., Feng, J.Q., Jing, D., Zhao, H., Kronenberg, H.M., Moore, D.C. and Yang, W. (2021). “Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis.” Bone Res 9(1): 6.

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The maturation and function of osteoblasts (OBs) rely heavily on the reversible phosphorylation of signaling proteins. To date, most of the work in OBs has focused on phosphorylation by tyrosyl kinases, but little has been revealed about dephosphorylation by protein tyrosine phosphatases (PTPases). SHP2 (encoded by PTPN11) is a ubiquitously expressed PTPase. PTPN11 mutations are associated with both bone and cartilage manifestations in patients with Noonan syndrome (NS) and metachondromatosis (MC), although the underlying mechanisms remain elusive. Here, we report that SHP2 deletion in bone gamma-carboxyglutamate protein-expressing (Bglap(+)) bone cells leads to massive osteopenia in both trabecular and cortical bones due to the failure of bone cell maturation and enhanced osteoclast activity, and its deletion in Bglap(+) chondrocytes results in the onset of enchondroma and osteochondroma in aged mice with increased tubular bone length. Mechanistically, SHP2 was found to be required for osteoblastic differentiation by promoting RUNX2/OSTERIX signaling and for the suppression of osteoclastogenesis by inhibiting STAT3-mediated RANKL production by osteoblasts and osteocytes. These findings are likely to explain the compromised skeletal system in NS and MC patients and to inform the development of novel therapeutics to combat skeletal disorders.

Jing, D., Li, C., Yao, K., Xie, X., Wang, P., Zhao, H., Feng, J.Q., Zhao, Z., Wu, Y. and Wang, J. (2021). “The vital role of Gli1(+) mesenchymal stem cells in tissue development and homeostasis.” J Cell Physiol.

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The hedgehog (Hh) signaling pathway plays an essential role in both tissue development and homeostasis. Glioma-associated oncogene homolog 1 (Gli1) is one of the vital transcriptional factors as well as the direct target gene in the Hh signaling pathway. The cells expressing the Gli1 gene (Gli1(+) cells) have been identified as mesenchymal stem cells (MSCs) that are responsible for various tissue developments, homeostasis, and injury repair. This review outlines some recent discoveries on the crucial roles of Gli1(+) MSCs in the development and homeostasis of varieties of hard and soft tissues.