Mapping and visualization of global research progress on mitophagy in osteoarthritis: A bibliometric analysis (2008–2024)

The Web of Science Core Collection (WoSCC) was employed to conduct a literature search from 2008 to 2024. Recognized as a comprehensive and authoritative database, the WoSCC provides access to high quality academic publications across diverse disciplines.The search formula utilized was: (((TS = (osteoarthritis)) OR TS = (osteoarthritis)) OR TS = (osteoarthrosis)) OR TS = (arthritis) AND (TS = (mitochondrial autophagy)) OR TS = (mitophagy). Only English-language publications were included, with a specific focus on articles among various document types. To minimize discrepancies resulting from database updates, literature retrieval was conducted on September 9, 2024. The screening process was undertaken by 2 independent reviewers, with any disagreements resolved through discussions to achieve consensus. [] ¹⁴

Three bibliometric tools were utilized for visualization and comprehensive analysis of academic data: VOSviewer 1.6.20, CiteSpace 6.3.R1, and R 4.3.3. VOSviewer, noted for its versatility, was crucial in mapping institutional and author collaborations, co-authorship, citation patterns, keyword co-occurrence networks, and co-citation networks.This tool facilitated the visualization and analysis of complex collaborative networks within academia. CiteSpace was employed to identify keyword bursts, facilitating an improved understanding of emerging trends and research hotspots. The parameters were established as follows: time slicing was defined from January 2008 to September 2024, with keywords selected as the node type. A keyword node threshold of 5 was applied prior to each fragment, and pruning was executed utilizing the pathfinder and clip merge network methods. Visualization analysis was conducted based on these parameters to generate a keyword timeline within the research field of mitophagy in osteoarthritis. The R 4.3.3 () was utilized for a thorough bibliometric analysis. This tool played a pivotal role in analyzing and mapping the global distribution of research output, uncovering significant trends and patterns, and assessing the impact of authors, journals, and institutions within the dataset. The H-index quantified the academic impact of individuals and journals, serving as a balanced measure of scholarly influence.Journal citation reports (JCR) quartiles and the impact factor (IF) were utilized to evaluate journal prestige and citation influence. JCR quartiles classify journals into 4 tiers, with Q1 indicating the highest academic impact, while the IF measures the average citations received by a journal's articles over the preceding 2 years. The most recent 2024 JCR and IF data were employed to ensure an up-to-date assessment of journal prestige and citation influence. [] ¹⁵ [,] ^{16 17} https://www.bibliometrix.org↗

The data screening process is depicted in Figure. The analysis revealed that 1679 authors from 924 distinct institutions across 41 countries and regions contributed to the 259 publications included in this study. These articles were disseminated across 140 different journals and collectively cited a total of 15,507 references. The annual number of publications pertaining to mitophagy in osteoarthritis research had exhibited a clear upward trend over the years (Fig.A). We applied a linear growth model with the equation: = 3.0833 − 12.515, resulting in an 푅value of 0.8441. This indicated a strong correlation between the number of publications and the years, reflecting an upward trend in research interest over time. Beginning with only a few publications around 2008, the field began to gain traction in the early 2010s, characterized by a gradual increase in the number of studies published each year. From 2016 onward, there was a notable acceleration in publication activity, signifying growing interest and advancements in this area. The period from 2020 to 2024 experienced a particularly significant increase, with the number of publications reaching 49 in 2024. This upward trajectory suggested that research on mitophagy in osteoarthritis is likely to continue expanding, thereby attracting sustained interest in the future (Fig.B). 1 2 2 y x 2

Among the most cited studies in this field was "," published in 2013 in(IF = 3.3). This influential article has garnered a total of 760 citations and provides comprehensive insights into the associations between pesticide exposure and chronic human diseases.Another highly cited work was "Aging and the pathogenesis of osteoarthritis," published in 2016 in Nature Reviews Rheumatology (IF = 29.4), which has accumulated 753 citations. This review examined the relationship between aging and the progression of osteoarthritis, contributing significantly to the field.This review examined the relationship between aging and the progression of osteoarthritis, contributing significantly to the field. Additionally, the third most cited article was "," published in 2014 in Annals of the Rheumatic Diseases (IF = 16.1), which has accumulated 742 citations. This research investigated the role of mitochondrial dysfunction in osteoarthritis, elucidating the underlying mechanisms of the disease. Pesticides and human chronic diseases: evidences, mechanisms, and perspectives Toxicology and Applied Pharmacology Age-related mitochondrial dysfunction and oxidative stress in osteoarthritis [] ¹⁸ [] ¹⁹ [] ²⁰

China was at the forefront of research on mitophagy in osteoarthritis, with a total of 159 publications. China ranked first in total publications (TP) (557) and total citations (TC) (3501), although it exhibited a relatively lower multiple country publications (MCP) ratio of 0.075, indicating a predominant focus on single-country publications. The United States followed with 35 publications, ranking second in both TP (116) and TC (3187). The USA also demonstrated a higher MCP ratio of 0.143, reflecting a greater level of international collaboration compared to China. Korea ranked third, with 14 publications and a similar citation count (988), exhibiting an MCP ratio of 0.143. Italy and Spain each had 6 publications, ranking fourth and fifth in TP, respectively, with notable MCP ratios Spain, in particular, possesses a ratio of 0.667, suggesting significant international collaborations. Other countries, such as Switzerland and Australia, also display high MCP ratios (0.500 and 0.667, respectively), indicating robust international research partnerships. Conversely, countries like Iran, despite having fewer publications, demonstrated a high average citation per publication (760 citations), underscoring the impact of their limited research output. The varying MCP ratios among countries reflected diverse approaches to international collaboration within this research domain (Fig.A, Table). The visualization map illustrating international collaborations among countries in mitophagy research related to osteoarthritis was presented. The USA was identified as having the highest number of collaborations, with a total link strength of 34. China followed closely, with a total link strength of 24. Australia also exhibited a notable presence, with a total link strength of 15 (Fig.B). 3 1 3

The 10 leading institutions in mitophagy research pertaining to osteoarthritis are depicted in FigureA. Wenzhou Medical University was at the forefront, with 25 published articles, underscoring its substantial contributions to this field. Southern Medical University in China occupied the second position, with 20 articles, reflecting its active engagement in the advancement of knowledge in this area. Universidade da Coruña follows with 16 articles, indicating its significant involvement in the research. FigureB illustrates the collaborative interactions among 45 institutions engaged in international partnerships, each contributing a minimum of 2 published articles in mitophagy research relevant to osteoarthritis. Sun Yat Sen University was notable for exhibiting the highest total link strength of 12, suggesting a robust collaborative network in this research domain. Southern Medical University closely trailed with a total link strength of 11, demonstrating its critical role in fostering research partnerships. Chang Gung University also exhibited strong international collaboration, with a link strength of 10, highlighting its influence and connectivity within the global research community. 4 4

A comprehensive overview of the top 20 most productive journals in the domain of mitophagy in osteoarthritis was presented (Table). "" is identified as the preeminent journal in this field, exhibiting an H-index of 9, an IF of 7.2, and a total of 13 publications. This positions it first in both TP and TC (710). The "" ranked second in TP with 9, though it is ranked ninth in TC (303), indicating a robust presence within the discipline.was positioned seventh in TP with 5, distinguished by its high IF (IF = 8.1), while it holds the 16th position in TC (186). The co-occurrence network of journals associated with mitophagy research in osteoarthritis (Fig.A). The 3 principal journals with the highest total link strength in this network were "" (71), "" (40), and "" (37). FigureB displays the journal coupling network diagram, wherein the 3 journals with the highest total link strength were "" (1557), "" (1116), and "Frontiers in Pharmacology" (856). 2 5 5 Osteoarthritis and Cartilage International Journal of Molecular Sciences Cell Death & Disease Osteoarthritis and Cartilage Arthritis & Rheumatology Autophagy Osteoarthritis and Cartilage Frontiers in Cell and Developmental Biology

The following was a list of the top 20 influential authors in the field of mitophagy research related to osteoarthritis. Jorg J. Goronzy leaded this cohort with an H-index of 5, a g-index of 5, and a high m-index of 0.83, reflecting his significant impact since he commenced his contributions in 2019. He ranked second in TP (5) and sixth in TC (248). Cornelia M. Weyand possessed a comparable profile, with an h-index and g-index of 5, an m-index of 0.83, and also 248 citations, resulting in her fourth position in citation rank. Francisco J. Blanco had also made notable contributions, evidenced by an h-index of 4, a g-index of 5, and a moderate m-index of 0.40 since 2015. He ranked first in total publication fraction (0.86) and 22nd in TC (158). Liu-Bryan, Ru, and Terkeltaub, Robert each had an h-index of 4 and are tied for second place in TC (702), underscoring their significant contributions to this research domain (Table). 3

The collaboration network comprised 15 authors who have participated in international partnerships, each having authored a minimum of 2 articles centered on mitophagy research in osteoarthritis. Ignacio Rego-Perez emerged as the most collaborative author, exhibiting a total link strength of 22, which indicated a robust and extensive network of international collaborations. Francisco J. Blanco closely followed, with a link strength of 21, reflecting his considerable collaborative contributions to the research community. Carlos Vaamonde Garcia also demonstrated significant collaborative engagement, with a total link strength of 18, highlighting his active involvement in promoting international research connections (Fig.). 6

A comprehensive keyword analysis of the selected articles identified 145 keywords, each occurring a minimum of 3 times. The primary keywords associated with mitophagy in osteoarthritis, the term "apoptosis" was particularly prominent, appearing 51 times with a total link strength of 283. Other significant keywords include "oxidative stress" and "activation," underscoring essential processes in osteoarthritis research. Additionally, keywords such as "mitochondrial dysfunction" (total link strength of 161) and "articular cartilage" (total link strength of 127) emphasized the focus on mechanisms that influence cartilage health in osteoarthritis studies (Table). 4

The visual analysis of the keyword co-occurrence network in mitophagy research related to osteoarthritis was present, the different colors indicated in the network represent the average publication year of various keywords. A total of 145 keywords with a minimum of 3 occurrences were identified. The shift from green (such as "mitochondrial dysfunction" and "oxidative stress") to yellow (like "biogenesis" and "senescence") illustrated the evolving research focus over time. More recent keywords, including "biogenesis," "fusion," and "senescence," are shown in yellow, representing their emergence in studies published around 2021 to 2022 (Fig.). A burst analysis of keywords revealed evolving trends in mitophagy research related to osteoarthritis (Fig.). The keyword "inhibition" experienced the most significant citation burst, reflecting a recent and growing interest in therapeutic interventions targeting inhibitory pathways. Since 2020, other keywords have shown notable bursts, indicating key areas of focus: "mTOR" and "induction" highlight the exploration of cellular growth and regulatory mechanisms; "cell death" underscores interest in apoptosis and related processes in osteoarthritis. Additionally, keywords such as "mechanisms," "parkin," "association," and "dysfunction" signaled a recent concentration on mitochondrial health and its implications for osteoarthritis. The terms "degeneration" and "chondrocyte senescence" indicated a sustained interest in understanding cartilage degradation and cellular aging. 7 8

This study analyzed 259 publications from 2008 to 2024. Research on mitophagy in osteoarthritis has shown a consistent upward trend since 2008, indicating a growing interest in mitochondrial dysfunction, oxidative stress, and their roles in osteoarthritis pathogenesis. China, particularly through institutions such as Wenzhou Medical University, has emerged as a leading contributor to research on mitophagy in osteoarthritis.This prominence reflects China's robust biomedical research infrastructure and the substantial population of osteoarthritis patients in the country, creating considerable demand for research in this area.China's collaborative research culture, integrating universities, hospitals, and research centers with advanced technologies like bioinformatics and molecular biology, has driven progress in osteoarthritis treatment, exemplified by Wenzhou Medical University's efforts, solidifying China's pivotal role in the field. [] ²¹ [] ²² [] ²³

In terms of authorship, Francisco J. Blanco stands out as one of the most prolific contributors. His team focuses on mitochondrial dysfunction and oxidative stress, which is critical for understanding the intricate cellular mechanisms underlying osteoarthritis. For example, Blanco et al demonstrates that diabetes exacerbates cartilage damage in osteoarthritis in mouse models and activating autophagy through inhibition of mammalian target of rapamycin (mTOR) effectively reduces cartilage degradation and synovial inflammation. This finding highlighted a specific cellular pathway that may be targeted for therapeutic intervention. [] ²⁴

A significant area of research in osteoarthritis focuses on cellular processes related to the disease, highlighting the critical roles of "apoptosis" and "oxidative stress" in osteoarthritis progression. Oxidative stress impairs mitochondrial function and disrupts autophagy, particularly in chondrocytes affected by osteoarthritis.This dysfunction is linked to increased mitochondrial damage and subsequent cellular death. Understanding mitochondrial health and dysfunction has become central to uncovering the cellular mechanisms underlying osteoarthritis, with related terms such as "mitochondrial dysfunction" and "biogenesis" gaining prominence. Research suggests that activating autophagy can protect human chondrocytes from mitochondrial dysfunction, highlighting its potential as a therapeutic target in osteoarthritis.Additionally, irisin, a myokine, has been found to upregulate mitochondrial biogenesis in chondrocytes, improving mitochondrial membrane potential and reducing oxidative damage. This protective mechanism is crucial for slowing osteoarthritis progression.This underscores an expand, underscoring a growing body of research investigating the therapeutic benefits of promoting mitochondrial health, particularly through mechanisms like mitophagy, in the context of osteoarthritis. [] ²⁵ [] ²⁶ [] ²⁷

Inflammation represents a critical area of investigation in osteoarthritis research, particularly in relation to its association with cartilage degradation. Terminology such as "cartilage," "articular cartilage," and "inflammation" underscores the imperative to explore the role of inflammation in the pathophysiology of osteoarthritis. The autophagic protein DEPP is integral to the regulation of mitophagy in response to pro-inflammatory cytokines, a process that is essential for preserving chondrocyte viability.Inflammatory responses in the joint environment can lead to cartilage tissue degradation, underscoring the significance of inflammation in osteoarthritis. [] ²⁸

Keyword burst analysis reveals trends and primary research interests in mitophagy in osteoarthritis over time. From 2020 to 2021, terms like "mTOR" and "cell death" highlight autophagy and apoptosis pathways, as research increasingly aims to uncover the cellular mechanisms influencing joint health. Inhibition of the phosphatidylinositol 3-kinase/AKT/mTOR pathway has been shown to enhance autophagy in osteoarthritis chondrocytes, leading to reduced inflammation and protection against cartilage degradation.Additionally, overexpression of sirtuin 3 can alleviate osteoarthritis symptoms by modulating the mTOR pathway, boosting autophagy while lowering apoptosis and inflammation.However, excessive autophagy may also contribute to cell death in cartilage affected by osteoarthritis,highlighting its context-dependent dual effects. [] ²⁹ [] ³⁰ [] ³¹

From 2021 to 2022, keywords such as "parkin," "dysfunction," and "inhibition" indicate a growing interest in mitochondrial quality in osteoarthritis. Parkin is crucial for removing damaged mitochondria in osteoarthritis chondrocytes, where it helps regulating reactive oxygen species levels and prevents apoptosis. This function is essential for maintaining chondrocyte viability under stress.Research involving 3-methyladenine, an autophagy inhibitor, has shown that inhibiting autophagy worsens cartilage degeneration in osteoarthritis. In experimental models, reduced autophagy has been linked to greater chondrocyte damage and cartilage loss, highlighting the protective role of autophagy in osteoarthritis.These findings emphasize the need to maintain mitochondrial integrity to preserve joint health. [] ³² [] ³³

From 2022 to 2024, the emergence of keywords like "degeneration" and "chondrocyte senescence" reflects recent interest in the degenerative processes associated with osteoarthritis, particularly regarding how cellular senescence affects chondrocytes. Aged chondrocytes increasingly exhibit a senescence-associated secretory phenotype, characterized by heightened inflammatory responses and oxidative stress. Enhancing autophagy may help mitigate these effects, potentially slowing osteoarthritis progression.Studies have shown that interventions aimed at boosting autophagy can reduce cellular senescence in osteoarthritis, thereby promoting chondrocyte survival and function. For example, fibroblast growth factor 21 has been shown to decrease senescence and apoptosis in osteoarthritis chondrocytes by activating autophagy.To reveal the intersection of aging and osteoarthritis, future study should focus on cartilage-specific degeneration mechanisms. [] ³⁴ [] ³⁵

In summary, several key areas may emerge as focal points for future studies. First, targeted mitochondrial therapies could become more prominent, aiming to clear damaged mitochondria in chondrocytes and reduce oxidative stress, potentially slowing osteoarthritis progression. Second, future research is likely to investigate how regulating autophagy can be used to diminish inflammatory processes, offering potential strategies for protecting joint health. Lastly, the integration of precision medicine approaches tailored to individual mitochondrial dysfunctions may refine treatment protocols, allowing for more personalized and effective therapies.