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Focal adhesion protein Kindlin-2 regulates bone homeostasis in mice 被引量:9
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作者 Huiling Cao Qinnan Yan +17 位作者 Dong Wang Yumei Lai Bo Zhou Qi Zhang Wenfei Jin simin lin Yiming Lei Liting Ma Yuxi Guo Yishu Wang Yilin Wang Xiaochun Bai Chuanju Liu Jian QFeng Chuanyue Wu Di Chen Xu Cao Guozhi Xiao 《Bone Research》 CAS CSCD 2020年第1期26-38,共13页
Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse Col... Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse Col1 a1-Cre transgene minimally impacts bone mass in mice, but deleting Kindlin-2 using the 10-kb mouse Dmp1-Cre transgene, which targets osteocytes and mature osteoblasts, results in striking osteopenia in mice. Kindlin-2 loss reduces the osteoblastic population but increases the osteoclastic and adipocytic populations in the bone microenvironment. Kindlin-2 loss upregulates sclerostin in osteocytes,downregulates β-catenin in osteoblasts, and inhibits osteoblast formation and differentiation in vitro and in vivo. Upregulation ofβ-catenin in the mutant cells reverses the osteopenia induced by Kindlin-2 deficiency. Kindlin-2 loss additionally increases the expression of RANKL in osteocytes and increases osteoclast formation and bone resorption. Kindlin-2 deletion in osteocytes promotes osteoclast formation in osteocyte/bone marrow monocyte cocultures, which is significantly blocked by an anti-RANKLneutralizing antibody. Finally, Kindlin-2 loss increases osteocyte apoptosis and impairs osteocyte spreading and dendrite formation.Thus, we demonstrate an important role of Kindlin-2 in the regulation of bone homeostasis and provide a potential target for the treatment of metabolic bone diseases. 展开更多
关键词 HOMEOSTASIS Kindlin cytes
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Orthogonal carbazole-perylene bisimide pentad:a photoconversion-tunable photosensitizer with diversified excitation and excited-state relaxation pathways 被引量:1
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作者 Zhaolong Wang Yue Sun +9 位作者 simin lin Gang Wang Xingmao Chang Xinyu Gou Taihong Liu Shengye Jin Gang He Yu-Chen Wei Pi-Tai Chou Yu Fang 《Science China Chemistry》 SCIE EI CSCD 2021年第12期2193-2202,共10页
Integrating multiple photosensitive properties into an“all-in-one”photosensitizer(PS)shows great promise for the treatment of cancers owing to synergistic effect among them.However,the development of such PSs,especi... Integrating multiple photosensitive properties into an“all-in-one”photosensitizer(PS)shows great promise for the treatment of cancers owing to synergistic effect among them.However,the development of such PSs,especially those that need a single laser source,remains a challenge.Herein,we report an orchestration of electron donors and acceptors in a propeller-like pentad,PBI-4Cz,where four carbazole(Cz)units are covalently linked to the ortho-positions of the perylene bisimide(PBI)core.Strong intramolecular donor-acceptor interaction significantly quenches the luminescence and largely extends the absorption spectra to near-infrared region.Excited-state dynamics investigated via femto-and nano-second transient absorption spectroscopy revealed exclusive charge separation of the PBI-4Cz within initial 0.5 ps when photoexcited regardless of which intermediate is involved.Energy dissipation of the resulting charge-separated state(PBI^(•−)-4Cz^(•−))is subjected to the toggle between intersystem-crossing toward excited triplet states and charge recombination toward ground states.Relative importance of the two pathways can be tuned by micro-environmental polarity,which endows PBI-4Cz remarkable performances of singlet-oxygen generation(>90.0%)in toluene and photothermal conversion(∼28.6%)in DMSO.Harnessing intrinsic photostability and excited-state processes of heavy-atom-free PBI derivatives not only holds a promise for multifunctional phototheranostics,but also provides a prototype for designing high-performance PSs with tunable photoconversion pathways. 展开更多
关键词 charge recombination charge separation perylene bisimide derivatives PHOTOSENSITIZERS singlet oxygen generation
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