Biomedicines最新文献_第6页

Rhythms in Remodeling: Posttranslational Regulation of Bone by the Circadian Clock.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030705

Vincent G Yuan

{"title":"Rhythms in Remodeling: Posttranslational Regulation of Bone by the Circadian Clock.","authors":"Vincent G Yuan","doi":"10.3390/biomedicines13030705","DOIUrl":"10.3390/biomedicines13030705","url":null,"abstract":"The circadian clock is a fundamental timekeeping system that regulates rhythmic biological processes in response to environmental light-dark cycles. In mammals, core clock genes (CLOCK, BMAL1, PER, and CRY) orchestrate these rhythms through transcriptional-translational feedback loops, influencing various physiological functions, including bone remodeling. Bone homeostasis relies on the coordinated activities of osteoblasts, osteoclasts, and osteocytes, with increasing evidence highlighting the role of circadian regulation in maintaining skeletal integrity. Disruptions in circadian rhythms are linked to bone disorders such as osteoporosis. Posttranslational modifications (PTMs), including phosphorylation, acetylation, and ubiquitination, serve as crucial regulators of both circadian mechanisms and bone metabolism. However, the specific role of PTMs in integrating circadian timing with bone remodeling remains underexplored. This review examines the intersection of circadian regulation and PTMs in bone biology, elucidating their impact on bone cell function and homeostasis. Understanding these interactions may uncover novel therapeutic targets for skeletal diseases associated with circadian disruptions.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fatty Acid Metabolism Provides an Essential Survival Signal in OxPhos and BCR DLBCL Cells.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030707

Aurélie Montagne, Konstantina Kotta, Karoline Kielbassa-Elkadi, Isabelle Martins, José Ángel Martinez-Climent, Guido Kroemer, Catherine Thieblemont, Véronique Baud

{"title":"Fatty Acid Metabolism Provides an Essential Survival Signal in OxPhos and BCR DLBCL Cells.","authors":"Aurélie Montagne, Konstantina Kotta, Karoline Kielbassa-Elkadi, Isabelle Martins, José Ángel Martinez-Climent, Guido Kroemer, Catherine Thieblemont, Véronique Baud","doi":"10.3390/biomedicines13030707","DOIUrl":"10.3390/biomedicines13030707","url":null,"abstract":"Backgroung/objectives: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of malignant lymphoma and is a heterogeneous disease with various gene and chromosomal abnormalities. The development of novel therapeutic treatments has improved DLBCL prognosis, but patients with early relapse or refractory disease have a poor outcome (with a mortality of around 40%). Metabolic reprogramming is a hallmark of cancer cells. Fatty acid (FA) metabolism is frequently altered in cancer cells and recently emerged as a critical survival path for cancer cell survival. Methods: We first performed the metabolic characterization of an extended panel of DLBCL cell lines, including lipid droplet content. Then, we investigated the effect of drugs targeting FA metabolism on DLBCL cell survival. Further, we studied how the combination of drugs targeting FA and either mitochondrial metabolism or mTOR pathway impacts on DLBCL cell death. Results: Here, we reveal, using a large panel of DLBCL cell lines characterized by their metabolic status, that targeting of FA metabolism induces massive DLBCL cell death regardless of their OxPhos or BCR/glycolytic subtype. Further, FA drives resistance of DLBCL cell death induced by mitochondrial stress upon treatment with either metformin or L-asparaginase, two FDA-approved antimetabolic drugs. Interestingly, combining inhibition of FA metabolism with that of the mTOR oncogenic pathway strongly potentiates DLBCL cell death. Conclusion: Altogether, our data highlight the central role played by FA metabolism in DLBCL cell survival, independently of their metabolic subtype, and provide the framework for the use of drugs targeting this metabolic vulnerability to overcome resistance in DLBCL patients.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nephrotoxicity of Immune Checkpoint Inhibitors in Single and Combination Therapy-A Systematic and Critical Review.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030711

Javier Tascón, Alfredo G Casanova, Laura Vicente-Vicente, Francisco J López-Hernández, Ana I Morales

{"title":"Nephrotoxicity of Immune Checkpoint Inhibitors in Single and Combination Therapy-A Systematic and Critical Review.","authors":"Javier Tascón, Alfredo G Casanova, Laura Vicente-Vicente, Francisco J López-Hernández, Ana I Morales","doi":"10.3390/biomedicines13030711","DOIUrl":"10.3390/biomedicines13030711","url":null,"abstract":"Background/Objectives: Immune checkpoint inhibitors (ICIs) have generated a revolutionary approach in the treatment of cancer, but their effectiveness has been compromised by immune-related adverse events, including renal damage. Although rare, these effects are relevant because they have been related to poor patient prognoses. The objective of this review was to estimate the current incidence of nephrotoxicity in patients treated with single and double ICI therapies. Methods: A total of 1283 potential articles were identified, which were reduced to 50 after applying the exclusion and inclusion criteria. Results: This study reveals the increase in acute kidney injury associated with these drugs in the last decade and shows that, interestingly, combined therapies with ICIs does not lead to an increase in kidney damage compared with anti-CTLA-4. It also suggests that kidney damage could be underdiagnosed when it comes to interstitial nephritis, because definitive evidence requires a renal biopsy. Conclusions: In perspective, these conclusions could guide clinicians in making decisions for therapy personalization and highlight the need to search for new diagnostic systems that are more sensitive and specific to the type of damage and could replace the biopsy.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

UBC4: A Repurposed Drug Regimen for Adjunctive Use During Bladder Cancer Treatment.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030706

Richard E Kast

{"title":"UBC4: A Repurposed Drug Regimen for Adjunctive Use During Bladder Cancer Treatment.","authors":"Richard E Kast","doi":"10.3390/biomedicines13030706","DOIUrl":"10.3390/biomedicines13030706","url":null,"abstract":"After it has metastasized, bladder cancer, the malignant transformation of the bladder urothelium, continues to be a common cause of death after maximal use of all currently available standard treatments. To address this problem in 2025, the drug repurposing movement within oncology aims to identify medicines in common general medical care use that have data indicating that they can interfere or inhibit a growth driving element that has been identified in bladder cancer. This paper now outlines extensive preclinical data showing that four drugs from general medical practice meet these criteria-the melatonergic drug ramelteon, the antidepressant fluoxetine, the antibiotic dapsone, and the analgesic drug celecoxib. This is the UBC4 regimen, meant as a possible adjunct added to standard treatments of metastatic bladder cancer. Three factors justify a clinical pilot trial of UBC4: (1) the UBC4 drugs are usually well tolerated and carry a low risk of harm, (2) the commonly fatal outcome of bladder cancer once it has widely metastasized, plus (3) the strong preclinical database showing UBC growth inhibition by each of the individual UBC4 drugs as outlined in this paper.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adipokines as Cardioprotective Factors: BAT Steps Up to the Plate.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030710

Keely McLeod, Victoria Datta, Scott Fuller

{"title":"Adipokines as Cardioprotective Factors: BAT Steps Up to the Plate.","authors":"Keely McLeod, Victoria Datta, Scott Fuller","doi":"10.3390/biomedicines13030710","DOIUrl":"10.3390/biomedicines13030710","url":null,"abstract":"Cardiovascular disease is the leading cause of death throughout most of the industrialized world. Metabolic syndrome (MetS) and its associated pathologies are underlying factors in the etiology of cardiovascular disease, as well as a plethora of other maladies which cause excess morbidity and mortality. Adipose tissue (AT) has come to be regarded as a bona fide endocrine organ which secretes specific molecular entities constituting part of a complex web of inter-organ crosstalk that functions as a key determinant of whole-body metabolic phenotype. Brown adipose tissue (BAT) has classically been regarded as a thermogenic tissue exerting its metabolic effects primarily through its capacity to oxidize substrates decoupled from ATP resynthesis, thereby resulting in increased energy expenditure (EE) and heat production. However, in recent years, BAT has begun to receive attention as a secretory organ in its own right. The molecules secreted specifically by BAT have been termed \"batokines\", and currently available evidence supports the notion that batokines exert favorable metabolic effects on multiple organ systems. While maintenance of healthy body composition by conferring resistance to excessive adiposity is a rather obvious mechanism by which BAT operates via increased EE, effects on critical organs such as the heart remain unclear. This narrative review focuses on four types of batokines (FGF21, neuregulin 4, 12,13-diHOME, and BAT-derived microRNAs) for which evidence of modulation of cardiovascular function exists in the context of pathological states such as hypertension, atherosclerosis, and ischemia/reperfusion injury. Given the overwhelming burden of cardiometabolic disease, further study of the functions of BAT and its secretome is warranted and will intensify in the future.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Molecular Basis of Polycystic Ovary Syndrome and Its Cardiometabolic Correlates: Exploring the Intersection and Its Clinical Implications-A Narrative Review.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030709

Jasmin Mahabamunuge, Nicole M Sekula, Christina Lepore, Meghana Kudrimoti, Animesh Upadhyay, Khadija Alshowaikh, Howard J Li, David B Seifer, Abdelrahman AlAshqar

{"title":"The Molecular Basis of Polycystic Ovary Syndrome and Its Cardiometabolic Correlates: Exploring the Intersection and Its Clinical Implications-A Narrative Review.","authors":"Jasmin Mahabamunuge, Nicole M Sekula, Christina Lepore, Meghana Kudrimoti, Animesh Upadhyay, Khadija Alshowaikh, Howard J Li, David B Seifer, Abdelrahman AlAshqar","doi":"10.3390/biomedicines13030709","DOIUrl":"10.3390/biomedicines13030709","url":null,"abstract":"Recent studies have highlighted the association between polycystic ovary syndrome (PCOS) and cardiometabolic diseases, leading to an improved understanding of the underlying mechanistic factors. PCOS significantly increases cardiovascular risk by predisposing individuals to various subclinical and clinical conditions, including atherosclerosis and type 2 diabetes mellitus. Additionally, it interacts synergistically with other traditional cardiovascular risk factors, such as obesity, hyperlipidemia, and insulin resistance. Several molecular mechanisms involving genetics, epigenetics, adipokine secretion, hyperandrogenemia, and hyperinsulinemia play a role in the relationship between PCOS and these comorbidities. For instance, androgen excess has been implicated in the development of hypertension, type 2 diabetes mellitus, endothelial dysfunction, and ultimately, broader cardiovascular disease. A deeper understanding of these underlying mechanisms facilitates the development of diagnostic, preventative, and therapeutic strategies directed at reducing cardiometabolic morbidity. This narrative review summarizes the current evidence, explores the potential clinical implications of these findings, and discusses emerging therapies to reduce cardiometabolic morbidity in women with PCOS.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut Microbiota in Different Treatment Response Types of Crohn's Disease Patients Treated with Biologics over a Long Disease Course.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030708

Xiaolei Zhao, Jun Xu, Dong Wu, Ning Chen, Yulan Liu

{"title":"Gut Microbiota in Different Treatment Response Types of Crohn's Disease Patients Treated with Biologics over a Long Disease Course.","authors":"Xiaolei Zhao, Jun Xu, Dong Wu, Ning Chen, Yulan Liu","doi":"10.3390/biomedicines13030708","DOIUrl":"10.3390/biomedicines13030708","url":null,"abstract":"Background and Aims: Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with a globally increasing prevalence, partially driven by alterations in gut microbiota. Although biological therapy is the first-line treatment for CD, a significant proportion of patients experience a primary non-response or secondary loss of response over time. This study aimed to explore the differences in gut microbiota among CD patients with divergent long-term responses to biological therapy, focusing on a long disease course. Methods: Sixteen CD patients who applied the biological agents for a while were enrolled in this study and were followed for one year, during which fecal specimens were collected monthly. Metagenomic analysis was used to determine the microbiota profiles in fecal samples. The response to biological therapy was evaluated both endoscopically and clinically. Patients were categorized into three groups based on their response: R (long-term remission), mA (mild active), and R2A group (remission to active). The differences in the gut microbiota among the groups were analyzed. Results: Significant differences in fecal bacterial composition were observed between the groups. The R2A group exhibited a notable decline in gut microbial diversity compared to the other two groups (p < 0.05). Patients in the R group had higher abundances of Akkermansia muciniphila, Bifidobacterium adolescentis, and Megasphaera elsdenii. In contrast, Veillonella parvula, Veillonella atypica, and Klebsiella pneumoniae were higher in the R2A group. Conclusions: Gut microbial diversity and specific bacterial significantly differed among groups, reflecting distinct characteristics between responders and non-responders.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thick-Filament-Based Regulation and the Determinants of Force Generation.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030703

Vivek P Jani, Weikang Ma

{"title":"Thick-Filament-Based Regulation and the Determinants of Force Generation.","authors":"Vivek P Jani, Weikang Ma","doi":"10.3390/biomedicines13030703","DOIUrl":"10.3390/biomedicines13030703","url":null,"abstract":"Background/Objectives: Thick-filament-based regulation in muscle is generally conceived as processes that modulate the number of myosin heads capable of force generation. It has been generally assumed that biochemical and structural assays of myosin active and inactive states provide equivalent measures of myosin recruitment, but recent studies indicate that this may not always be the case. Here, we studied the steady-state and dynamic mechanical changes in skinned porcine myocardium before and after treatment with omecamtiv mecarbil (OM) or piperine to help decipher how the biochemical and structural states of myosin separately affect contractile force. Methods: Force-Ca2+ relationships were obtained from skinned cardiomyocytes isolated from porcine myocardium before and after exposure to 1 μM OM and 7 μM piperine. Crossbridge kinetics were acquired using a step response stretch activation protocol allowing myosin attachment and detachment rates to be calculated. Results: OM augmented calcium-activated force at submaximal calcium levels that can be attributed to increased thick filament recruitment, increases in calcium sensitivity, an increased duty ratio, and from decelerated crossbridge detachment resulting in slowed crossbridge cycling kinetics. Piperine, in contrast, was able to increase activated force at submaximal calcium levels without appreciably affecting crossbridge cycling kinetics. Conclusions: Our study supports the notion that thick filament activation is primarily a process of myosin recruitment that is not necessarily coupled with the chemo-cycling of crossbridges. These new insights into thick filament activation mechanisms will need to be considered in the design of sarcomere-based therapies for treatment of myopathies.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atrial Fibrillation Begets Atrial Fibrillation in Small Animals: Characterization of New Rat Model of Spontaneous Atrial Fibrillation.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-13 DOI: 10.3390/biomedicines13030704

Alkora Ioana Balan, Vasile Bogdan Halaţiu, Dan Alexandru Cozac, Emilian Comșulea, Cosmin Constantin Mutu, Ioana Aspru, Delia Păcurar, Claudia Bănescu, Marcel Perian, Alina Scridon

{"title":"Atrial Fibrillation Begets Atrial Fibrillation in Small Animals: Characterization of New Rat Model of Spontaneous Atrial Fibrillation.","authors":"Alkora Ioana Balan, Vasile Bogdan Halaţiu, Dan Alexandru Cozac, Emilian Comșulea, Cosmin Constantin Mutu, Ioana Aspru, Delia Păcurar, Claudia Bănescu, Marcel Perian, Alina Scridon","doi":"10.3390/biomedicines13030704","DOIUrl":"10.3390/biomedicines13030704","url":null,"abstract":"Background/Objectives: We previously described a rat model of AF induced by long-term transesophageal atrial burst pacing. Here, we further characterize this model by exploring arrhythmia inducibility, spontaneous AF occurrence, and related autonomic and molecular changes. Methods: Twelve adult male Wistar rats were randomized into two groups: control (n = 5) and AF (n = 7). The rats in the AF group underwent 10 days of transesophageal atrial pacing. In the control rats, the same protocol was mimicked. Spontaneous AF occurrence and heart rate variability (HRV) were evaluated before, during, and after stimulation. Left atrial RNA levels of Hcn1, Hcn2, Hcn4, and Pitx2 were evaluated. Results: In AF, no animal presented spontaneous AF before stimulation. After stimulation initiation, all AF rats presented spontaneous AF (p = 0.08). In the AF rats, HRV analysis revealed a progressive increase in the standard deviation of the RR intervals after atrial stimulation initiation (p < 0.01). The left atrial RNA levels of Hcn4 were higher (p = 0.03) and Pitx2 levels were lower (p = 0.02) in the AF rats compared to the control group. Conclusions: This study validates our previous data and confirms the occurrence of spontaneous AF following long-term atrial pacing in rats. Relatively increased parasympathetic modulation and changes in the atrial expression of Hcn4, encoding for If, and Pitx2 likely play critical mechanistic roles in this model.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prg4 and Osteoarthritis: Functions, Regulatory Factors, and Treatment Strategies.

IF 3.9 3区工程技术

Biomedicines Pub Date : 2025-03-12 DOI: 10.3390/biomedicines13030693

Peng-Jie Fu, Sheng-Yuan Zheng, Yan Luo, Zhuo-Qun Ren, Zi-Han Li, Ya-Ping Wang, Bang-Bao Lu

{"title":"Prg4 and Osteoarthritis: Functions, Regulatory Factors, and Treatment Strategies.","authors":"Peng-Jie Fu, Sheng-Yuan Zheng, Yan Luo, Zhuo-Qun Ren, Zi-Han Li, Ya-Ping Wang, Bang-Bao Lu","doi":"10.3390/biomedicines13030693","DOIUrl":"10.3390/biomedicines13030693","url":null,"abstract":"Proteoglycan 4 (PRG4), also known as lubricin, plays a critical role in maintaining joint homeostasis by reducing friction between articular cartilage surfaces and preventing cartilage degradation. Its deficiency leads to early-onset osteoarthritis (OA), while overexpression can protect against cartilage degeneration. Beyond its lubricating properties, PRG4 exerts anti-inflammatory effects by interacting with Toll-like receptors, modulating inflammatory responses within the joint. The expression of Prg4 is regulated by various factors, including mechanical stimuli, inflammatory cytokines, transcription factors such as Creb5 and FoxO, and signaling pathways like TGF-β, EGFR, and Wnt/β-catenin. Therapeutic strategies targeting PRG4 in OA have shown promising results, including recombinant PRG4 protein injections, gene therapies, and small molecules that enhance endogenous Prg4 expression or mimic its function. Further research into the molecular mechanisms regulating Prg4 expression will be essential in developing more effective OA treatments. Understanding the interplay between Prg4 and other signaling pathways could reveal novel therapeutic targets. Additionally, advancements in gene therapy and biomaterials designed to deliver PRG4 in a controlled manner may hold potential for the long-term management of OA, improving patient outcomes and delaying disease progression.","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0