Article
Biology
Dezhi Zhao, Manuel A. Riquelme, Teja Guda, Chao Tu, Huiyun Xu, Sumin Gu, Jean X. Jiang
Summary: This study demonstrates the critical role of osteocytic Cx43 hemichannels in the anabolic function of bone in response to mechanical loading. Inhibition of hemichannels impeded the response of osteoblast activity and bone formation to mechanical loading, suggesting that targeting osteocytic Cx43 hemichannels could be a potential therapeutic strategy for bone loss and osteoporosis.
Article
Geriatrics & Gerontology
Senbo An, Shengyuan Zheng, Zijun Cai, Siyu Chen, Chen Wang, Yusheng Li, Zhenhan Deng
Summary: This article summarizes the function of Connexin43 in musculoskeletal tissues and its abnormal expression in related disorders. Studies have shown that Connexin43 plays an important role in bone homeostasis regulation. By forming gap junctions and hemichannels, Connexin43 can participate in cellular regulation and signaling. This article highlights the importance of Connexin43 as a potential target for the treatment of related bone and muscle disorders and emphasizes the need for further research.
Article
Biochemistry & Molecular Biology
Jin Kono, Masakatsu Ueda, Atsushi Sengiku, Sylvia O. Suadicani, Osamu Ogawa, Hiromitsu Negoro
Summary: The study suggests that urothelial Cx43 mediated ATP signaling and coordination of urothelial activity are essential for proper perception and regulation of responses to bladder distension in the animals' awake, active phase. This research highlights the significant role of Cx43 in bladder function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Sonia Nasi, Mariela Castelblanco, Veronique Chobaz, Driss Ehirchiou, Alexander So, Ilaria Bernabei, Teruo Kusano, Takeshi Nishino, Ken Okamoto, Nathalie Busso
Summary: Pathologic calcification of cartilage is associated with aging and cartilage injury, potentially accelerating osteoarthritis. Xanthine oxidoreductase (XOR), particularly its XO form, may contribute to chondrocyte mineralization and pathological calcification in osteoarthritis cartilage.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Meng Chen, Guobin Li, Lan Zhang, Kaiting Ning, Baoqiang Yang, Jean X. Jiang, Dong-En Wang, Huiyun Xu
Summary: Osteocytes can release small molecules through Cx43 channels, affecting metabolic pathways related to inflammation and oxidative stress. This study identified potential metabolites released by osteocytes through Cx43 channels, providing new insights into the regulatory mechanisms of osteocytes on themselves and other cells.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Axelle Cooreman, Anne Caufriez, Andres Tabernilla, Raf Van Campenhout, Kaat Leroy, Prashant Kadam, Julen Sanz Serrano, Bruna dos Santos Rodrigues, Pieter Annaert, Mathieu Vinken
Summary: This study investigated the effects of several drugs proposed for treating COVID-19 on Cx43 hemichannels. The results showed that a combination of lopinavir and ritonavir, as well as remdesivir, reduced Cx43 mRNA levels, but none of the drugs affected Cx43 protein expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xunshan Ren, Huangming Zhuang, Bin Li, Fuze Jiang, Yuelong Zhang, Panghu Zhou
Summary: Excessive mechanical strain is a prominent risk factor for osteoarthritis, and the underlying molecular mechanism contributing to mechanical signaling transduction remains unclear. In this study, the role of Piezo1, a mechanosensitive ion channel, in osteoarthritis development was investigated. It was found that up-regulated expression of Piezo1 in osteoarthritis cartilage contributed to chondrocyte apoptosis. Inhibition of Piezo1 with Gsmtx4 in mouse models ameliorated the progression of osteoarthritis and accelerated cartilage matrix production by inhibiting chondrocyte apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kouji Fukuyama, Motohiro Okada
Summary: The study found that three mood-stabilizing atypical antipsychotics, clozapine, quetiapine, and brexpiprazole, enhance tripartite synaptic glutamatergic transmission by enhancing astroglial Cx43 containing hemichannel activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Kouji Fukuyama, Motohiro Okada
Summary: The study revealed that the effects of zotepine on astroglial L-glutamate release are concentration-dependent and time-dependent, likely through Akt signaling pathway activation leading to enhanced function of astroglial hemichannels, ultimately resulting in increased L-glutamate release. These findings suggest that enhanced astroglial L-glutamatergic transmission induced by zotepine is partially involved in its mood-stabilising and proconvulsive actions.
Review
Medicine, General & Internal
Tomasz Szponder, Michal Latalski, Anna Danielewicz, Katarzyna Krac, Aleksandra Kozera, Beata Drzewiecka, Dominika Nguyen Ngoc, Dominika Dobko, Joanna Wessely-Szponder
Summary: Osteoarthritis (OA) is a chronic, progressive disease characterized by the loss of articular cartilage in middle-aged and older patients. The immune system plays a pivotal role in the pathogenesis of OA, with both humoral and cellular mediators contributing to cartilage destruction and joint inflammation. Animal models are widely used to study the disease and potential therapies. This review provides an overview of OA signs, pathogenesis, and classification, as well as discussing the advantages and disadvantages of different animal models. Treatment options include mesenchymal stem cells, gene therapies, and blood-derived products, along with tissue engineering techniques and biomaterials.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Motohiro Okada, Kouji Fukuyama, Takashi Shiroyama, Yuto Ueda
Summary: The study investigated the effects of brivaracetam on astroglial L-glutamate release and the interaction with SV2A and Cx43 expression. The results suggest that suppression of TNF-α-induced neuronal excitability by inhibiting ectopic SV2A contributes to the antiepileptic/anticonvulsive mechanism of brivaracetam action.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Olivia E. Crouthamel, Leping Li, Michael T. Dilluvio, Thomas W. White
Summary: Mutations in the GJA1 gene encoding connexin43 (Cx43) have been linked to various rare genetic disorders, including those affecting the skin. This study investigated the functional consequences of a specific Cx43 mutation (Cx43-G38E) associated with a novel human phenotype. The research showed that the mutation increased the activity of hemichannels, suggesting a potential role in skin and skeletal disorders caused by Cx43 mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Yi Zhu
Summary: Connexin43 is a crucial protein in the family that not only plays a critical role in gap junctions but also has various functions independent of gap junctions. It forms different-sized polypeptides through distinct mechanisms and functions in different cellular compartments. Research on Connexin43 will enhance our understanding of how genes increase their functions and may guide the development of therapies for metabolic conditions, cancer, and other diseases.
Article
Biotechnology & Applied Microbiology
Paolo Caravaggi, Elisa Assirelli, Andrea Ensini, Maurizio Ortolani, Erminia Mariani, Alberto Leardini, Simona Neri, Claudio Belvedere
Summary: This study aims to investigate the impact of cyclic joint loading on cartilage metabolism, identify mechanisms for preventing or slowing down OA progression, and provide preliminary data on its application. The proposed protocol integrates biomechanical data, medical imaging, and molecular information to analyze human OA knee cartilage explants with different degrees of degeneration. The comprehensive analysis is expected to provide new insights on the beneficial effects of physiological loading and contribute to the design of non-pharmacological treatments for limiting OA progression.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Anatomy & Morphology
Seiji Shimomura, Hiroaki Inoue, Yuji Arai, Shuji Nakagawa, Yuta Fujii, Tsunao Kishida, Masaharu Shin-Ya, Shohei Ichimaru, Shinji Tsuchida, Osam Mazda, Kenji Takahashi
Summary: HIF-1α plays a significant role in regulating aggrecan and ADAM-TS5 expression in articular cartilage under hypoxia and general mechanical stimulation. The study showed that mechanical stimulation under hypoxia enhances HIF-1α and aggrecan expression, with nuclear translocation of HIF-1α, while also significantly reducing ADAM-TS5 expression. Furthermore, HIF-1α is crucial for maintaining cartilage homeostasis.
Review
Endocrinology & Metabolism
Rui Hua, Jingruo Zhang, Manuel A. Riquelme, Jean X. Jiang
Summary: Oxidative stress plays a significant role in affecting the function of connexin channels and bone loss, with increased opening of connexin hemichannels under oxidative stress conditions providing cell protection. Additionally, oxidative stress decreases osteocyte viability and impairs communication among osteocytes.
CURRENT OSTEOPOROSIS REPORTS
(2021)
Article
Biology
Zhen Li, Sumin Gu, Yumeng Quan, Kulandaiappan Varadaraj, Jean X. Jiang
Summary: Using recombinant retroviruses containing pathogenic genes for congenital cataracts, injected into embryonic chick lenses, closely mimicked the process of cataract formation and provided a reliable in vivo system for studying the development and underlying mechanisms of cataracts and other genetic diseases.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yumeng Quan, Yu Du, Yuxin Tong, Sumin Gu, Jean X. Jiang
Summary: The lens uses connexin channels to maintain its redox homeostasis, but oxidative stress may lead to dysfunction of gap junction channels and hemichannels, thereby inducing cataract formation.
Article
Biochemistry & Molecular Biology
Yumeng Quan, Yu Du, Changrui Wu, Sumin Gu, Jean X. Jiang
Summary: Our study reveals that Cx43 hemichannels (HCs) in lens epithelial cells play a crucial role in protecting the lens against oxidative stress by facilitating the exchange of oxidants and antioxidants, thereby maintaining redox homeostasis. Activation of Cx43 HCs by oxidative stress results in a reduction of intracellular reactive oxygen species (ROS) accumulation and regulation of anti-oxidative gene expression, contributing to preventing cataract formation during aging.
Article
Biochemistry & Molecular Biology
Guobin Li, Lan Zhang, Zhe Lu, Baoqiang Yang, Hui Yang, Peng Shang, Jean X. Jiang, Dong'en Wang, Huiyun Xu
Summary: The roles of Cx43-based gap junctions and hemichannels in bone and muscle aging are investigated in this study, which found that enhancement of Cx43 hemichannels reduces bone mass and promotes muscle collagen synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yan Zeng, Manuel A. Riquelme, Rui Hua, Jingruo Zhang, Francisca M. Acosta, Sumin Gu, Jean X. Jiang
Summary: This study found that mechanical stress activates intracellular Ca2+ through Piezo1 channels, which regulates the opening of Cx43 hemichannels (HCs) mediated by PI3K-Akt signaling. The opened Cx43 HCs, together with other channels, sustain the intracellular Ca2+ signal, leading to bone anabolic function.
CELL AND BIOSCIENCE
(2022)
Article
Biology
Jingruo Zhang, Manuel A. Riquelme, Rui Hua, Francisca M. Acosta, Sumin Gu, Jean X. Jiang
Summary: This study reveals a new role of mitochondrial Cx43 and hemichannels in modulating mitochondrial function and homeostasis in bone osteocytes under oxidative stress. Through mediating K+, H+, and ATP transfer across the mitochondrial inner membrane and interacting with mitochondrial ATP synthase, mtCx43 hemichannels regulate mitochondrial ATP generation and contribute to the maintenance of mitochondrial redox levels in response to oxidative stress.
Article
Multidisciplinary Sciences
Yu Du, Yuxin Tong, Yumeng Quan, Guangyan Wang, Hongyun Cheng, Sumin Gu, Jean X. Jiang
Summary: Cataract is a major cause of blindness worldwide. The study found that protein kinase A (PKA) activation increases gap junction communication, reducing oxidative stress-induced cataracts and reactive oxygen species (ROS) levels. PKA activation also protects lens fiber cells from oxidative stress-induced death through hemichannel-mediated glutathione transport. Deletion of connexins, the proteins responsible for gap junctions, leads to increased lens opacity and reduced anti-oxidative stress gene expression. In summary, PKA activation via increased connexin channels alleviates cataracts by reducing ROS levels and cell death.
Article
Biology
Kazuki Inoue, Yongli Qin, Yuhan Xia, Jie Han, Ruoxi Yuan, Jun Sun, Ren Xu, Jean X. Jiang, Matthew B. Greenblatt, Baohong Zhao
Summary: Adipoq-lineage progenitors in bone marrow are the main cellular source of M-CSF, producing much higher levels than osteoblast lineage cells. Deficiency of M-CSF in these progenitors significantly reduces the generation of bone marrow macrophages and osteoclasts, leading to severe osteopetrosis.
Article
Immunology
Benjamin Voisin, Vinod Nadella, Thomas Doebel, Shubham Goel, Keiko Sakamoto, Otgonzaya Ayush, Jay-Hyun Jo, Michael C. Kelly, Tetsuro Kobayashi, Jean X. Jiang, Ying Hu, Chunhua Yan, Keisuke Nagao
Summary: Hypodermal macrophages (HDMs) play an important role in Staphylococcus aureus infections. Different subsets of HDMs were identified based on CCR2 expression, which were regulated by fibroblast-derived growth factor CSF1. Loss of CCR2- HDMs led to the accumulation of hyaluronic acid (HA), and HDM-mediated HA clearance required the HA receptor LYVE-1. Cell-autonomous IGF1 was necessary for the expression of LYVE-1. Remarkably, the absence of HDMs or IGF1 limited Staphylococcus aureus expansion via HA and provided protection against cellulitis.
Article
Cell Biology
Jerry P. Chen, Rong Li, Jean X. Jiang, Xiao-Dong Chen
Summary: Recently, the dual effects of mesenchymal stem cells (MSCs) on tumorigenesis have raised concerns. We hypothesized that contact inhibition in confluent MSCs leads to the production of effector molecules that can suppress tumor cell growth. Our results showed that co-culturing or treating tumor cells with conditioned media from confluent MSCs inhibited tumor cell growth more significantly than with sub-confluent MSCs. Subcutaneous tumor formation was completely prevented by inoculating tumor cells mixed with the conditioned media. This suggests that soluble anti-tumor effectors produced by confluent MSCs could be used as cell-free therapeutics, addressing concerns associated with cell-based therapies.
Article
Biochemical Research Methods
Yu Du, Francisca M. Acosta, Jianping Zhang, Yuxin Tong, Yumeng Quan, Sumin Gu, Jean X. Jiang
Summary: This protocol provides a detailed description of altering Cx hemichannel function in primary chicken lens fiber cells using high-titer retroviral infection, as well as assessing protective measures against oxidative stress.
Article
Cell & Tissue Engineering
Dezhi Zhao, Rui Hua, Manuel A. Riquelme, Hongyun Cheng, Teja Guda, Huiyun Xu, Sumin Gu, Jean X. Jiang
Summary: This study reveals the significant role of osteocytic integrin alpha 5 in the anabolic response of bone to mechanical loading. Deletion of integrin alpha 5 gene results in increased osteocyte apoptosis and reduced anabolic responses to tibial compression, including decreased osteoblasts and bone formation, and increased osteoclasts and bone resorption. This study suggests that integrin alpha 5 could be a potential therapeutic target for bone loss, especially in the elderly population with decreased mechanical sensitivity.
Article
Biochemical Research Methods
Yuting Li, Francisca M. Acosta, Yumeng Quan, Zhen Li, Sumin Gu, Jean X. Jiang
Summary: This study presents a method for inducing macrophage activation and fibrotic tissue formation within the eye using a combination of growth factor injection and immunofluorescence. The protocol allows for the evaluation of macrophage distribution and quantification of fibrotic tissue formation.
Article
Cell & Tissue Engineering
Manuel A. Riquelme, Sumin Gu, Rui Hua, Jean X. Jiang
Summary: Mechanical loading activates integrin alpha 5 and alpha V, leading to the opening of connexin 43 (Cx43) hemichannels (HCs) and release of bone anabolic factors. Inhibition of integrin alpha V affects HCs opening and disrupts PI3K/AKT signaling pathway, while integrin alpha 5 activation is dependent on PI3K/AKT activation. Dendritic alpha V is a more sensitive mechanosensor than alpha 5 in activating HCs at low fluid shear stress levels.