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Mandujano-Lázaro G, Torres-Rojas MF, Ramírez-Moreno E, Marchat LA. Virtual screening combined with molecular docking for the !identification of new anti-adipogenic compounds. Sci Prog 2025; 108:368504251320313. [PMID: 39936374 PMCID: PMC11815789 DOI: 10.1177/00368504251320313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/13/2025]
Abstract
Obesity is an important risk factor for diabetes, cardiovascular diseases, and cancer, reducing the quality of life and expectancy of millions of people. Consequently, obesity has turned into one of the most health public problems worldwide, which highlights the urgent need for new and safe treatments. Obesity is mainly related to excessive fat accumulation; therefore, proteins participating in white adipose tissue increase and dysfunction are considered pertinent and attractive targets for developing new methods that can help with body weight control. In this context, virtual screening of libraries containing a large number of molecules represents a valuable strategy for the identification of potential anti-adipogenic compounds with reduced costs and time production. Here, we review the scientific literature about the prediction of new ligands of specific proteins through molecular docking and virtual screening of chemical libraries, with the aim of proposing new potential anti-adipogenic molecules. First, we present the targets related to adipogenesis and adipocyte functions that were selected for the following studies: PPARγ, Crif1, SIRT1, ERβ, PC1, FTO, Mss51, and FABP4. Then, we describe the obtention of new ligands according to the characteristics of the virtual screening approach, i.e. a structure-based drug design (SBDD) or a ligand-based drug design (LBDD). Finally, the critical analysis of these computational strategies and the corresponding results points out the necessity of combining computational and in vitro or in vivo assays for the identification of effective new anti-adipogenic molecules for obesity control. It also evidences that translating molecular docking and virtual screening results into successful drug candidates for adipogenesis and obesity control remains a huge challenge.
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Affiliation(s)
- Gilberto Mandujano-Lázaro
- Laboratorio de Biomedicina Molecular 2, ENMH, Instituto Politécnico Nacional, Ciudad de México, México
| | - María F Torres-Rojas
- Laboratorio de Biomedicina Molecular 2, ENMH, Instituto Politécnico Nacional, Ciudad de México, México
| | - Esther Ramírez-Moreno
- Laboratorio de Biomedicina Molecular 2, ENMH, Instituto Politécnico Nacional, Ciudad de México, México
| | - Laurence A Marchat
- Laboratorio de Biomedicina Molecular 2, ENMH, Instituto Politécnico Nacional, Ciudad de México, México
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翁 敬, 高 俊, 李 敏, 韦 嘉, 张 少, 兰 桂, 李 冰, 覃 丹, 黄 波, 朱 振, 苏 小, 彭 雅, 瞿 申, 邱 前. [Effect of endoscopic surgery combined with chemotherapy and radiotherapy on prognosis of early nasopharyngeal carcinoma patients in high incidence area]. LIN CHUANG ER BI YAN HOU TOU JING WAI KE ZA ZHI = JOURNAL OF CLINICAL OTORHINOLARYNGOLOGY, HEAD, AND NECK SURGERY 2024; 38:472-476;484. [PMID: 38858110 PMCID: PMC11480587 DOI: 10.13201/j.issn.2096-7993.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Indexed: 06/12/2024]
Abstract
Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinoma（T1-2N₀M₀） who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy group（n=34, treated with endoscopic surgery combined with chemotherapy） and the surgery + radiotherapy group（n=34, treated with endoscopic surgery combined with radiotherapy）. Propensity score matching was used to match the patient data between the two groups at a 1∶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groups（all P>0.05）. The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groups（both P>0.05）. After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group （all P> 0.05） Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.
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Affiliation(s)
- 敬锦 翁
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 俊潇 高
- 南方医科大学珠江医院耳鼻咽喉科Department of Otolaryngology, Zhujiang Hospital, Southern Medical University
| | - 敏 李
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 嘉章 韦
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 少杰 张
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 桂萍 兰
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 冰 李
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 丹雪 覃
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 波 黄
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 振潮 朱
- 南方医科大学珠江医院耳鼻咽喉科Department of Otolaryngology, Zhujiang Hospital, Southern Medical University
| | - 小妹 苏
- 广东省人民医院耳鼻咽喉头颈外科Department of Otolaryngology Head and Neck Surgery, Guangdong Provincial People's Hospital[Guangdong Academy of Medical Sciences], Southern Medical University
| | - 雅琪 彭
- 广东省人民医院耳鼻咽喉头颈外科Department of Otolaryngology Head and Neck Surgery, Guangdong Provincial People's Hospital[Guangdong Academy of Medical Sciences], Southern Medical University
| | - 申红 瞿
- 广西壮族自治区人民医院耳鼻咽喉头颈外科(南宁，530021)Department of Otolaryngology Head and Neck Surgery, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - 前辉 邱
- 广东省人民医院耳鼻咽喉头颈外科Department of Otolaryngology Head and Neck Surgery, Guangdong Provincial People's Hospital[Guangdong Academy of Medical Sciences], Southern Medical University
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Jiang YZ, Hu LY, Chen MS, Wang XJ, Tan CN, Xue PP, Yu T, He XY, Xiang LX, Xiao YN, Li XL, Ran Q, Li ZJ, Chen L. GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines. World J Stem Cells 2024; 16:538-550. [PMID: 38817334 PMCID: PMC11135246 DOI: 10.4252/wjsc.v16.i5.538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/12/2024] [Accepted: 04/12/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.
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Affiliation(s)
- Yang-Zhou Jiang
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Lan-Yue Hu
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Mao-Shan Chen
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Xiao-Jie Wang
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Cheng-Ning Tan
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Pei-Pei Xue
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Teng Yu
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Xiao-Yan He
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Li-Xin Xiang
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Yan-Ni Xiao
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Xiao-Liang Li
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Qian Ran
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Zhong-Jun Li
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China
| | - Li Chen
- Laboratory of Radiation Biology, Department of Blood Transfusion, Laboratory Medicine Center, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China
- Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Chongqing 400037, China.
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Xiang L, Li F, Xiang Y, Zhang W, Shi D, Zhang X, Chen L, Ran Q, Li Z. CR6-Interacting Factor-1 Promotes Osteoclastogenesis Through the NF-κB Signaling Pathway after Irradiation. Radiat Res 2023; 200:489-502. [PMID: 37815199 DOI: 10.1667/rade-22-00066.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/11/2023] [Indexed: 10/11/2023]
Abstract
Radiation exposure arising from radiotherapy may induce rapid bone loss and an increase in the extent of bone resorption. Reactive oxygen species (ROS) caused by radiation exposure play a crucial role during the process of osteoclastogenesis. However, the pathological mechanisms underlying radiation-induced osteoclastogenesis have yet to be fully elucidated. CR6-interacting factor-1 (Crif1) as a multifunctional protein is involved in regulating multiple biological functions in cells. Here, we investigated the role of Crif1 in radiation-induced osteoclastogenesis and found that radiation exposure induced an increase in the expression level of Crif1 and enhanced osteoclastogenesis in osteoclast progenitors. Crif1 and NF-κB p65 co-localized in the cytoplasm after radiation exposure. Crif1 knockdown did not affect the phosphorylation and total protein levels of extracellular signal-regulated kinases (ERK), c-Jun amino (N)-terminal kinases (JNK), p38, and IκB-α before and after irradiation. However, Crif1 knockdown did lead to the reduced phosphorylation and nuclear translocation of NF-κB p65 after irradiation and resulted in a reduced level of osteoclastogenesis in RAW264.7 cells after irradiation. In vivo studies involving Lyz2Cre;Crif1fl/fl mice possessing the myeloid-specific deletion of Crif1 demonstrated the alleviation of bone loss after irradiation when compared with Crif1fl/fl mice. Our findings demonstrate that Crif1 mediated the phosphorylation and nuclear translocation of NF-κB p65 and promoted osteoclastogenesis via the NF-κB signaling pathway after radiation exposure. Thus, our analysis revealed a specific role for Crif1 in the mediation of radiation-induced bone loss and may provide new insight into potential therapeutic strategies for radiation-induced bone loss.
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Affiliation(s)
- Lixin Xiang
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Fengjie Li
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Yang Xiang
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Weiwei Zhang
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Dongling Shi
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Xiaomei Zhang
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Li Chen
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Qian Ran
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
| | - Zhongjun Li
- Basic Research Innovation Center for Acute Radiation Syndrome, Laboratory Medicine Center, Department of Blood Transfusion, Lab of Radiation Biology, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China
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Xu X, Zhao L, Terry PD, Chen J. Reciprocal Effect of Environmental Stimuli to Regulate the Adipogenesis and Osteogenesis Fate Decision in Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs). Cells 2023; 12:1400. [PMID: 37408234 PMCID: PMC10216952 DOI: 10.3390/cells12101400] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 05/02/2023] [Accepted: 05/12/2023] [Indexed: 07/07/2023] Open
Abstract
Mesenchymal stem cells derived from bone marrow (BM-MSCs) can differentiate into adipocytes and osteoblasts. Various external stimuli, including environmental contaminants, heavy metals, dietary, and physical factors, are shown to influence the fate decision of BM-MSCs toward adipogenesis or osteogenesis. The balance of osteogenesis and adipogenesis is critical for the maintenance of bone homeostasis, and the interruption of BM-MSCs lineage commitment is associated with human health issues, such as fracture, osteoporosis, osteopenia, and osteonecrosis. This review focuses on how external stimuli shift the fate of BM-MSCs towards adipogenesis or osteogenesis. Future studies are needed to understand the impact of these external stimuli on bone health and elucidate the underlying mechanisms of BM-MSCs differentiation. This knowledge will inform efforts to prevent bone-related diseases and develop therapeutic approaches to treat bone disorders associated with various pathological conditions.
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Affiliation(s)
- Xinyun Xu
- Department of Nutrition, The University of Tennessee, Knoxville, TN 37996, USA
| | - Ling Zhao
- Department of Nutrition, The University of Tennessee, Knoxville, TN 37996, USA
| | - Paul D. Terry
- Department of Medicine, Graduate School of Medicine, The University of Tennessee, Knoxville, TN 37920, USA;
| | - Jiangang Chen
- Department of Public Health, The University of Tennessee, Knoxville, TN 37996, USA
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Jiang Y, Xiang Y, Lin C, Zhang W, Yang Z, Xiang L, Xiao Y, Chen L, Ran Q, Li Z. Multifunctions of CRIF1 in cancers and mitochondrial dysfunction. Front Oncol 2022; 12:1009948. [PMID: 36263222 PMCID: PMC9574215 DOI: 10.3389/fonc.2022.1009948] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 09/14/2022] [Indexed: 11/23/2022] Open
Abstract
Sustaining proliferative signaling and enabling replicative immortality are two important hallmarks of cancer. The complex of cyclin-dependent kinase (CDK) and its cyclin plays a decisive role in the transformation of the cell cycle and is also critical in the initiation and progression of cancer. CRIF1, a multifunctional factor, plays a pivotal role in a series of cell biological progresses such as cell cycle, cell proliferation, and energy metabolism. CRIF1 is best known as a negative regulator of the cell cycle, on account of directly binding to Gadd45 family proteins or CDK2. In addition, CRIF1 acts as a regulator of several transcription factors such as Nur77 and STAT3 and partly determines the proliferation of cancer cells. Many studies showed that the expression of CRIF1 is significantly altered in cancers and potentially regarded as a tumor suppressor. This suggests that targeting CRIF1 would enhance the selectivity and sensitivity of cancer treatment. Moreover, CRIF1 might be an indispensable part of mitoribosome and is involved in the regulation of OXPHOS capacity. Further, CRIF1 is thought to be a novel target for the underlying mechanism of diseases with mitochondrial dysfunctions. In summary, this review would conclude the latest aspects of studies about CRIF1 in cancers and mitochondria-related diseases, shed new light on targeted therapy, and provide a more comprehensive holistic view.
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Affiliation(s)
- Yangzhou Jiang
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Yang Xiang
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Chuanchuan Lin
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Weiwei Zhang
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Zhenxing Yang
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Lixin Xiang
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Yanni Xiao
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Li Chen
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Qian Ran
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
| | - Zhongjun Li
- Laboratory of Radiation Biology, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, China
- State Key Laboratory of Trauma, Burn and Combined Injuries, The Second Affiliated Hospital, Army Medical University, Chongqing, China
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Liu P, Tu J, Wang W, Li Z, Li Y, Yu X, Zhang Z. Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts. Front Bioeng Biotechnol 2022; 10:830722. [PMID: 35252138 PMCID: PMC8893233 DOI: 10.3389/fbioe.2022.830722] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
Osteoclasts and osteoblasts play a major role in bone tissue homeostasis. The homeostasis and integrity of bone tissue are maintained by ensuring a balance between osteoclastic and osteogenic activities. The remodeling of bone tissue is a continuous ongoing process. Osteoclasts mainly play a role in bone resorption, whereas osteoblasts are mainly involved in bone remodeling processes, such as bone cell formation, mineralization, and secretion. These cell types balance and restrict each other to maintain bone tissue metabolism. Bone tissue is very sensitive to mechanical stress stimulation. Unloading and loading of mechanical stress are closely related to the differentiation and formation of osteoclasts and bone resorption function as well as the differentiation and formation of osteoblasts and bone formation function. Consequently, mechanical stress exerts an important influence on the bone microenvironment and bone metabolism. This review focuses on the effects of different forms of mechanical stress stimulation (including gravity, continuously compressive pressure, tensile strain, and fluid shear stress) on osteoclast and osteoblast function and expression mechanism. This article highlights the involvement of osteoclasts and osteoblasts in activating different mechanical transduction pathways and reports changings in their differentiation, formation, and functional mechanism induced by the application of different types of mechanical stress to bone tissue. This review could provide new ideas for further microscopic studies of bone health, disease, and tissue damage reconstruction.
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Affiliation(s)
- Pan Liu
- School of Clinical Medicine, Chengdu Medical College, Chengdu, China
- The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Ji Tu
- Spine Labs, St. George & Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Wenzhao Wang
- Department of Orthopedics, West China Hospital of Sichuan University, Chengdu, China
| | - Zheng Li
- People’s Hospital of Jiulongpo District, Chongqing, China
| | - Yao Li
- School of Clinical Medicine, Chengdu Medical College, Chengdu, China
- The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Xiaoping Yu
- School of Public Health, Chengdu Medical College, Chengdu, China
- Basic Medical College of Chengdu University, Chengdu, China
- *Correspondence: Xiaoping Yu, ; Zhengdong Zhang,
| | - Zhengdong Zhang
- School of Clinical Medicine, Chengdu Medical College, Chengdu, China
- The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
- *Correspondence: Xiaoping Yu, ; Zhengdong Zhang,
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Chen K, Jiao Y, Liu L, Huang M, He C, He W, Hou J, Yang M, Luo X, Li C. Communications Between Bone Marrow Macrophages and Bone Cells in Bone Remodeling. Front Cell Dev Biol 2020; 8:598263. [PMID: 33415105 PMCID: PMC7783313 DOI: 10.3389/fcell.2020.598263] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 11/27/2020] [Indexed: 01/15/2023] Open
Abstract
The mammalian skeleton is a metabolically active organ that continuously undergoes bone remodeling, a process of tightly coupled bone resorption and formation throughout life. Recent studies have expanded our knowledge about the interactions between cells within bone marrow in bone remodeling. Macrophages resident in bone (BMMs) can regulate bone metabolism via secreting numbers of cytokines and exosomes. This review summarizes the current understanding of factors, exosomes, and hormones that involved in the communications between BMMs and other bone cells including mensenchymal stem cells, osteoblasts, osteocytes, and so on. We also discuss the role of BMMs and potential therapeutic approaches targeting BMMs in bone remodeling related diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma.
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Affiliation(s)
- Kaixuan Chen
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Yurui Jiao
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Ling Liu
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Mei Huang
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Chen He
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Wenzhen He
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Jing Hou
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Mi Yang
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China
| | - Xianghang Luo
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
| | - Changjun Li
- Department of Endocrinology, Endocrinology Research Center, The Xiangya Hospital of Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.,Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
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