Academic publishing is the support for dissemination of research findings that constitute the grounds upon which new orientations and improvements are based on sharing breaking ideas, critical analyses of data, and argumentations that sustain the development of collaborative research projects. The wide diffusion of new scientific findings is pivotal to the progress of medical sciences, a salient feature of human societal fullness and intellectual welfare. In a practical way, the value of academic publishing can be ascertained by its capacity to reach a wide number of readers from different fields that may provide the soil for interactive projects. The challenges are numerous (Zul in Challenges in Academic Publishing; Navigating the Obstacles, 2023). An examination of the means developed to survey the individual performances of scientists, based on their publications, has led me to comment in this editorial on pitfalls that muddle the way to upstanding evaluations mainly based on irrelevant metrics.
Cellular signaling is generally understood as the support of communication between contiguous cells belonging to the same tissue or cells being far apart of each other, at a molecular scale, when the message emitted by the transmitters is traveling in liquid or solid matter to reach recipient targets. Subcellular signaling is also important to ensure the proper cell constitution and functioning. However cell signaling is mostly used in the first understanding, to describe how the message sent from one point to another one, will reach a target where it will be interpreted. The Cellular Communication Network (CCN) factors (Perbal et al. 2018) constitute a family of biological regulators thought to be responsible for signaling pathways coordination (Perbal 2018). Indeed, these proteins interact with a diverse group of cell receptors, such as integrins, low density lipoprotein receptors, heparan sulfate proteoglycan receptors (HSPG), and the immunoglobulin superfamily expressed exclusively in the nervous system, or with soluble factors such as bone morphogenetic proteins (BMPS) and other growth factors such as vascular endothelial growth factor, fibroblastic growth factor, and transforming growth factor (TGFbeta). Starting from the recapitulation of basic concepts in enzymology and protein-ligands interactions, we consider, in this manuscript, interpretations of the mechanistic interactions that have been put forward to explain the diversity of CCN proteins biological activities. We suggest that the cross-talks between superfamilies of proteins under the control of CCNs might play a central role in the coordination of developmental signaling pathways.
Cellular communication network factor (CCN) 3, which is one of the founding members of the CCN family, displays diverse functions. However, this protein generally represses the proliferation of a variety of cells. Along with skeletal development, CCN3 is produced in cartilaginous anlagen, growth plate cartilage and epiphysial cartilage. Interestingly, CCN3 is drastically induced in the growth plates of mice lacking CCN2, which promotes endochondral ossification. Notably, chondrocytes in these mutant mice with elevated CCN3 production also suffer from impaired glycolysis and energy metabolism, suggesting a critical role of CCN3 in cartilage metabolism. Recently, CCN3 was found to be strongly induced by impaired glycolysis, and in our study, we located an enhancer that mediated CCN3 regulation via starvation. Subsequent investigations specified regulatory factor binding to the X-box 1 (RFX1) as a transcription factor mediating this CCN3 regulation. Impaired glycolysis is a serious problem, resulting in an energy shortage in cartilage without vasculature. CCN3 produced under such starved conditions restricts energy consumption by repressing cell proliferation, leading chondrocytes to quiescence and survival. This CCN3 regulatory system is indicated to play an important role in articular cartilage maintenance, as well as in skeletal development. Furthermore, CCN3 continues to regulate cartilage metabolism even during the aging process, probably utilizing this regulatory system. Altogether, CCN3 seems to prevent "overwork" by chondrocytes to ensure their sustainable life in cartilage by sensing energy metabolism. Similar roles are suspected to exist in relation to systemic metabolism, since CCN3 is found in the bloodstream.
In celebration of the twentieth anniversary of the inception of the CCN society, and of the first post-Covid-19 live meeting, the executive board of the ICCNS had chosen Nice as the venue for the 11th International workshop on the CCN family of genes. On this occasion participation in the meeting was extended to colleagues from other cell signaling fields who were invited to present both an overview of their work and the future directions of their laboratory. Also, for the first time, the members of the JCCS Editorial Board were invited to participate in a JCCS special session during which all aspects of the journal « life ¼ were addressed and opened to free critical discussion. The scientific presentations and the discussions that followed showed once more that an expansion of the session topics was beneficial to the quality of the meeting and confirmed that the ARBIOCOM project discussed last April in Nice was now on track to be launched in 2023. The participants unanimously welcomed Professor Attramadal's proposition to organize the 2024, 12th International CCN workshop in Oslo, Norway.
It is a renewed pleasure to wish our authors, editorial board members, and readership an excellent new year, full of professional and personal satisfactions. According to the Chinese Horoscope, 2023, the Year of Water Rabbit, is predicted to be quiet; a year to step back, assess the situation and make plans. It will be the time to carefully appraise, with the patience of the Water Rabbit, the future and scientific wealth of our Journal. Based on a few aspects of the CCN3 biology status that remain open questions, I am presenting below a short summary of a few CCN research directions that in my eyes, become necessary to undertake through wide-angle collaborative approaches.
According to Chinese astrology, the Tiger is considered as the king of all animals. The Year of the Tiger 2022 was meant to symbolize determinism, vitality, strength, spontaneity and novelty, with the water element making it wiser and thoughtful. Often associated with the defeat of evil, a Water Tiger year occurs only every 60 years. The 2022 version was indeed a year of resilience, even in the time of conflict and the struggles that we have faced both in personal and professional realms. It was a good time to reflect in order to overcome all challenges and difficulties. The revamping of both the International CCN society (ICCNS) and the Journal of Cell Communication and Signaling (JCCS) that I had previously initiated and officially announced in 2019, are on track to becoming a successful reality and will be pursued over the coming years, thanks to the strong support of our colleagues, members of the JCCS Editorial board and representatives of other scientific societies who support our efforts to broaden the scope of the ICCNS and its communication organ. I will schematically draw below the guidelines that we intend to follow in the near future.
A little over a year ago, on January 25, 2021, the new Editor-in-Chief (EiC) of JCCS stated in his Editorial: "ICCNS and JCCS were the brainchildren of Bernard Perbal, and without his energy and drive, neither would exist, to the detriment of us who are driven to solve difficult problems in science, and not picking low-hanging fruit. All one has to do is examine all the editorials written in JCCS (and CCS!) to see evidence of this. It will be tough to fill those shoes."I disagree with the assertion in the Editorial published on March 29, 2022 that G. Martin contributed "to the initial growth of the International CCN Society, and, ultimately, to the establishment of this journal." My opinion is based on the evidence that the International CCN Society (ICCNS) and its official organ journal, the Journal of Cell Communication and Signaling (JCCS), were created by myself. Over a span of 21 years until the present, and in spite of his contribution to the early history of CTGF, we never heard from G. Martin being involved or interested in any aspect of the ICCNS and its biannual meetings, nor in any aspect in the growth of JCCS.In order to further clarify the confusion stemming from the Editorial in question and to give credit where it is due, I provide below detailed evidence that undoubtedly ascribes the true inception of both ICCNS and JCCS, and merit to the efforts of all those who trusted and supported us during the initial difficult creative moments.I am of the opinion that the Editorial, and the implications that it carries do not justice to the efforts of those who were really involved in the creation of both the ICCNS and JCCS.In the name of respectful scientific integrity, I will provide the evidence that correctly attributes the inception of ICCNS and JCCS.
In this editorial I briefly review the new JCCS scientific directions that have emerged from the complicated situations created by the pandemics of COVID- 19, and by the internal audit of both Journal of Cell Communication and Signaling and International CCN Society, that were initiated since my proposal at the 2019 International Workshop on the CCN family of genes.I also welcome the distinguished members of our renewed JCCS Editorial and congratulate all those who have in many different ways participated to the consolidation of the 2021 JCCS Impact Factor attaining 5.908.
Systems that have yet to stand the test of time carry imperfections that need to be skillfully addressed with the least amount of authoritarianism as possible. The communication and transmission of knowledge that we hold dear are essential pillars to social progress. As such, it is necessary to analyze with the greatest scientific objectivity the applications arising from the deep revolution rooted in the total sequencing of the human genome which affects all aspects of our societies. This extraordinary advance in human knowledge and the resulting technological achievements should not lend themselves to the fears or fantasies often fueled by those who criticize all scientific progress calling into question the most established dogmas. Certain supposedly scholarly analyses of the health situation with which we are currently confronted worldwide are a perfect illustration of this unfortunate trend. It is undeniable that the progress of molecular genetics has opened up a wide range of applications in many fields, affecting the well-being of humans, their mental and physical health. The apparent universal and individual interest for the most advanced genetic profile analyzing technologies is a testimony to this strong common desire to better understand one's genetic heritage and to control their usage. Despite this movement, little attention is given to the recent advances in genetics applied to essential aspects of the social life of individuals through their inter-personal interactions. It is particularly distressing that the contributions of molecular biology and genetics to the daily well-being of individuals have not yet allowed open-access non-medical genetic testing to gain the recognition it deserves and are still viewed as recreational applications. Through an analysis of the cross influences that genetic biotechnologies have had since the beginning of the century in the fields of nutrition and cosmetics, we have tried to project ourselves into the near future which should witness major behavioral and social upheavals.
The recent increase of the Journal of Cell Signaling and Communication' 2020 Impact Factor to 5.782, and its growing audience in the scientific community, provides an opportunity to step back and look at different aspects of this indicator's value. The take home message is that the top-ten major contributions to the 2020 ranking originated from North America and Europe followed by India with a high percentage of CCN-related publications and an excellent proportion of Editorial Board members' contributions to the Top10 best citations for the 2018-2019 period.
Cellular communication network factor (CCN) 3 is one of the classical members of the CCN family, which are characterized by common molecular structures and multiple functionalities. Although this protein was discovered as a gene product overexpressed in a truncated form in nephroblastoma, recent studies have revealed its physiological roles in the development and homeostasis of mammalian species, in addition to its pathological association with a number of diseases. Cartilage is a tissue that creates most of the bony parts and cartilaginous tissues that constitute the human skeleton, in which CCN3 is also differentially produced to exert its molecular missions therein. In this review article, after the summary of the molecular structure and function of CCN3, recent findings on the regulation of ccn3 expression and the roles of CCN3 in endochondral ossification, cartilage development, maintenance and disorders are introduced with an emphasis on the metabolic regulation and function of this matricellular multifunctional molecule.
Since the authors first reviewed this subject in 2016 significant progress has been documented in the CCN field with advances made in the understanding of how members of the CCN family of proteins, CCN1-6, contribute to the pathogenesis and progression, positive and negative, of a larger variety of cancers. As termed matricellular proteins, and more recently the connective communication network, it has become clearer that members of the CCN family interact complexly with other proteins in the extracellular microenvironment, membrane signaling proteins, and can also operate intracellularly at the transcriptional level. In this review we expand on this earlier information providing new detailed information and insights that appropriate a much greater involvement and importance of their role in multiple aspects of cancer. Despite all the new information many more questions have been raised and intriguing results generated that warrant greater investigation. In order to permit the reader to smoothly integrate the new information we discuss all relevant CCN members in the context of cancer subtypes. We have harmonized the nomenclature with CCN numbering for easier comparisons. Finally, we summarize what new has been learned and provide a perspective on how our knowledge about CCN1-6 is being used to drive new initiatives on cancer therapeutics.
BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. METHODS: CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. RESULTS: Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-ß versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. CONCLUSIONS: This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS.
Interferon-beta/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/metabolism , Natalizumab/therapeutic use , Nephroblastoma Overexpressed Protein/biosynthesis , Adult , Aged , Aged, 80 and over , Brain/drug effects , Brain/metabolism , Cohort Studies , Disease Progression , Female , Humans , Male , Middle Aged , Nephroblastoma Overexpressed Protein/genetics , Treatment Outcome
CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3-/- mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.
Central Nervous System/metabolism , Demyelinating Diseases/etiology , Gene Expression Regulation , Nephroblastoma Overexpressed Protein/genetics , Remyelination/genetics , Animals , Brain/metabolism , Brain/pathology , Disease Models, Animal , Fluorescent Antibody Technique , Mice , Myelin Sheath/metabolism , Nephroblastoma Overexpressed Protein/metabolism , Oligodendrocyte Precursor Cells/metabolism , Oligodendroglia/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology
