Search Results (76)

Ultrasound-guided hydrodissection and dextrose prolotherapy have evolved into anatomically explicit but mechanistically distinct strategies for musculoskeletal pain. This State-of-the-Art narrative review aimed to synthesize major recent clinical and technical developments and to interpret them within a target-based framework. PubMed and Embase via Ovid were searched for English-language publications from 1 January 2021 through 29 July 2026, supplemented by selected pre-2021 landmark studies identified through backward citation tracking. After initial deduplication, 1662 records entered Title/Abstract screening. The final narrative synthesis cited 67 publications, including selected landmark and methodological sources. One author performed screening, and a second author reviewed the final publication selection; study selection was purposive and designed for a narrative synthesis rather than exhaustive systematic inclusion. Four questions guided the review: recent refinements in hydrodissection technique and indications; increasing condition specificity of prolotherapy evidence; areas of overlap and distinction between the two procedures; and the evidentiary status of emerging applications. Hydrodissection research remains concentrated in carpal tunnel syndrome and increasingly addresses injectate, volume, tissue-plane spread, and procedural configuration, whereas evidence beyond the carpal tunnel remains incompletely replicated. Prolotherapy research has shifted from broad claims toward condition-specific studies in tendinopathy, plantar fasciopathy, knee osteoarthritis, periarticular disorders, and temporomandibular joint pathology. Across both fields, variations in concentration, volume, anatomical site, session number, comparator, rehabilitation, and procedural expertise limit generalization. Hydrodissection is defined by observable, fluid-mediated separation of a tissue interface, whereas prolotherapy involves dextrose delivery to a symptomatic connective-tissue target without requiring immediate tissue-plane separation. The proposed framework is intended to standardize terminology, organize evidence maturity, and guide future comparative research rather than prescribe a validated treatment algorithm. Full article

Objectives: To systematically evaluate the diagnostic accuracy, clinical applicability, and methodological maturity of artificial intelligence (AI)-based methods for temporomandibular disorders (TMD), temporomandibular joint (TMJ) abnormalities, and related cranio-cervico-mandibular (CCM) musculoskeletal conditions compared with conventional diagnostic methods and accepted reference standards. Materials and Methods: This systematic review and exploratory diagnostic test accuracy meta-analysis was conducted in accordance with PRISMA 2020 and PRISMA-DTA. The protocol was retrospectively registered in PROSPERO (CRD420261428138). PubMed/MEDLINE, Embase, and Scopus were searched from database inception through February 2026. Eligibility for the primary synthesis was restricted to published studies in English or Spanish involving adults aged 18 years or older. All extracted records were re-audited article by article to align the evidence with the diagnostic question. The domain-specific quantitative synthesis was restricted to TMJ osteoarthritis studies with explicit 2 × 2 diagnostic data or a unique, verifiable reconstruction from reported class totals and sensitivity/specificity. Risk of bias was assessed with QUADAS-2. Results: From 1471 records identified, 174 entered the master extraction dataset. After reclassification, 84 records were retained for primary TMD/TMJ qualitative synthesis, 8 as secondary CCM musculoskeletal evidence, 31 as conventional or reference standard supporting evidence, 33 as methodological or contextual evidence, 4 as differential orofacial pain evidence, and 14 as excluded or minimal-background records. Twenty-one studies were assessed as potential diagnostic accuracy candidates. Three TMJ osteoarthritis studies contributed to the domain-specific exploratory meta-analysis: two with explicit 2 × 2 data and one with a reproducible reconstruction. Pooled sensitivity was 0.791 (95% CI: 0.700–0.861) and pooled specificity was 0.869 (95% CI: 0.811–0.911). Heterogeneity was substantial for sensitivity (I² = 68.2%) and moderate for specificity (I² = 57.3%). Conclusions: AI demonstrates promising performance in selected image-based TMJ osteoarthritis tasks. Nevertheless, the evidence remains exploratory because only three studies were quantitatively comparable, one table was reconstructed, and modalities and validation designs differed. AI should be interpreted as an augmentative decision support tool rather than a replacement for MRI, CBCT, or validated clinical frameworks such as DC/TMD. Clinical Relevance: AI may support image-based TMD/TMJ workflows, but present evidence does not justify autonomous diagnosis or replacement of established clinical and imaging reference standards. Full article

Introduction/Objectives: Temporomandibular joint osteoarthritis (TMJOA) causes pain, mandibular dysfunction, fibrocartilage degradation, and synovial inflammation. Current therapies are mainly palliative and limited by rapid intra-articular clearance and insufficient disease-modifying effects. This review summarizes injectable hydrogels for TMJOA as regenerative scaffolds, drug delivery systems, joint lubricants, and mechanical buffers. Methods: Relevant studies were identified from PubMed/MEDLINE, Web of Science and Google Scholar using terms related to TMJOA, injectable hydrogels, intra-articular delivery, tissue engineering, cartilage repair, lubrication, viscosupplementation and mechanical buffering. Studies were selected if they addressed hydrogel design, biological function, mechanical performance, biosafety or translational evaluation. Results: Injectable hydrogels have been investigated mainly as bioactive regenerative scaffolds and acellular functional biomaterials. Bioactive systems may regulate inflammation and oxidative stress, deliver cells, exosomes, drugs or growth factors, and support fibrocartilage repair. Acellular systems primarily aim to improve intra-articular retention, lubrication, viscoelastic adaptation and mechanical buffering. However, current evidence remains largely preclinical, with limited validation of long-term residence, degradation behavior, TMJ-specific mechanical performance, repeat dosing, biosafety and functional outcomes. Conclusions: Injectable hydrogels represent promising multifunctional platforms for TMJOA treatment. Cell-, exosome-, and growth factor-loaded systems show regenerative potential but face manufacturing, safety, regulatory, and long-term validation challenges. Acellular multifunctional hydrogels may be more feasible for near-term translation. Clinical Significance: Injectable hydrogels may provide minimally invasive, locally sustained treatment for TMJOA by integrating symptom control, microenvironment modulation, and mechanical adaptation. Full article

Background/Objectives: Although the etiology and pathomechanism of temporomandibular joint osteoarthritis (TMJ OA) and rheumatoid arthritis (RA) are different, they can both lead to serious structural and functional changes in the masticatory system. This study aimed to assess and compare the prevalence and characteristics of functional changes in the masticatory system in RA and OA TMJ patients. Materials and Methods: This cross-sectional study included 40 RA patients meeting the 2010 ACR/EULAR criteria and 40 TMJ OA patients. Research diagnostic criteria for TMD (RDC/TMD) were used to assess functional changes. Results: Orofacial pain was a predominant TMD reported in 80% of RA patients and in 67.5% of OA TMJ patients. There was no difference in the orofacial pain intensity and degree of somatization between RA and OA TMJ patients (p = 0.114). Orofacial pain duration was statistically longer in OA TMJ patients than in RA patients (p = 0.003). The ranges of mandibular movement were limited but without any statistically significant differences between the groups compared for maximum active opening (p = 0.349) and maximum passive opening (p = 0.461). Patients with RA presented with more muscles affected with pain. The most painful muscles were the medial pterygoid muscles and the anterior belly of the digastric muscle for the right side (p = 0.006) and for the left side (p = 0.004), and the tendon of the temporal muscle (p = 0.011) and (p = 0.004). The pain intensity of these muscles was statistically higher in RA patients in comparison to OA TMJ patients. Predominant TMJ sounds were slight crepitations in both RA and OA TMJ patients, mainly during laterotrusion in OA (p = 0.000). Conclusions: Laterotrusion was the key movement differentiating TMD manifestations between the two groups. Early functional diagnosis of the temporomandibular joint and an interdisciplinary therapeutic approach, combining treatment of the underlying disease with therapy of the masticatory system disorders, are crucial to limit the progression of changes and improve masticatory function. Full article

Mandibular condylar cartilage (MCC) exhibits greater susceptibility to mechanical stress-induced degeneration than tibial articular cartilage (TAC). This study investigated whether differential epigenetic regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of antioxidant responses, is associated with distinct antioxidant capacities between these cartilage types. Cartilage tissues from 5-week-old male ICR mice (n = 16 for gene analyses, n = 8 for protein analyses) were obtained using laser microdissection. Gene and protein expression was analyzed by microarray, real-time RT-PCR, and immunohistochemistry. DNA methylation of the Nrf2 promoter was evaluated using pyrosequencing and high-resolution melting analysis. Nrf2 expression in MCC was approximately 1/10 that in TAC at mRNA level and only 5% at protein level. Downstream antioxidant enzymes (NQO1, G6PD, HO-1) showed significantly reduced expression in MCC. Oxidative DNA damage marker 8-OHdG was significantly elevated in MCC compared to TAC (20.0% vs. 10.7%, p < 0.05). The Nrf2 promoter region showed higher DNA methylation levels in MCC, confirmed by high-resolution melting analysis. Higher Nrf2 promoter methylation in MCC is associated with reduced antioxidant capacity and elevated oxidative damage. This epigenetic–antioxidant relationship may contribute to MCC’s vulnerability to mechanical stress-induced degeneration and represents a potential therapeutic target for temporomandibular joint disorders. Full article

Background/Objectives: Intra-articular injections are used for temporomandibular disorders (TMDs) resistant to conservative treatment. However, many reviews assess injectable agents combined with arthrocentesis or other co-interventions, limiting interpretation of their standalone effects. This overview aimed to summarize meta-analytic evidence on standalone intra-articular injections for temporomandibular joint disorders. Methods: MEDLINE, BASE, and Europe PMC were searched on 29 March 2026. Systematic reviews with quantitative meta-analyses evaluating standalone intra-articular TMJ injections were included. Data regarding injectable substances, clinical indications, and outcome domains were extracted and synthesized descriptively. Results: Three systematic reviews with meta-analyses were included. The evidence addressed platelet-rich plasma, corticosteroids, sodium hyaluronate, and physiological saline. Reported indications included degenerative joint disease, osteoarthritis, internal derangement, and arthritis. All included agents were reported to be associated with pain reduction. Conclusions: Meta-analytic evidence on standalone intra-articular injections for TMDs remains limited and heterogeneous. Available data suggest potential benefits, mainly for pain reduction, but do not establish clear superiority of any agent. The potential therapeutic activity of physiological saline should be considered when designing future injection trials. Full article

Background and Objectives: Temporomandibular disorders (TMDs) encompass a broad spectrum of functional and structural abnormalities of the temporomandibular joint (TMJ). Conventional diagnostic tools, although essential, often fail to capture the underlying biochemical mechanisms driving disease progression. Synovial fluid (SF), by virtue of its direct proximity to intra-articular tissues, represents an accessible biological matrix for identifying molecular signatures of inflammation, cartilage degradation, lubrication failure, oxidative stress, and angiogenic activation. The objective of this review is to synthesize current evidence on SF proteomics in TMD and evaluate its potential translational value in precision medicine. Materials and Methods: A narrative review of the literature was conducted on PubMed to identify human studies focused on SF proteomic and biochemical biomarkers in TMD. Eligible studies included original research articles assessing SF composition in relation to specific TMJ pathologies, diagnostic categories, or clinical phenotypes. Extracted data included study design, sample characteristics, analytic methodology, biomarkers investigated, and key findings. Google Gemini (Google LLC, Mountain View, CA, USA) was used as an AI-assisted tool to support language editing and manuscript writing during the preparation of this article. The use of this tool was limited to linguistic refinement; all scientific content, data interpretation, and conclusions were formulated and verified by the authors. Results: Across the analyzed studies, TMD phenotypes—particularly disc displacement with or without reduction (DDwR, DDwoR) and osteoarthritis (OA)—were characterized by consistent alterations in cytokines (IL-1β, IL-6, IL-8, TNF-α), extracellular matrix (ECM) components (aggrecan, glycosaminoglycans (GAGs), decorin, MMP-2, MMP-9), lubrication molecules (lubricin/PRG4), oxidative stress mediators (myeloperoxidase (MPO), nitric oxide (NO), glutathione peroxidase (GPX)), adipokines (chemerin, resistin, adiponectin), and angiogenic factors (vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2)). Recent liquid chromatography–tandem mass spectrometry (LC–MS/MS) analyses further revealed phenotype-specific protein clusters and pathways related to inflammation, ferroptosis, hypoxia signaling, and proteoglycan metabolism. Conclusions: Current evidence suggests that SF proteomics and multi-analyte biomarker profiling offer a promising, hypothesis-generating approach for understanding the biological mechanisms underlying TMD. The integration of proteomic, metabolic, and inflammatory markers holds future potential for diagnostic panel development; however, prospective clinical validation is still required before SF-based molecular profiling can be implemented as a precision medicine tool in TMJ disorders. Full article

Lubricin, also known as proteoglycan 4 (PRG4), is a key glycoprotein involved in boundary lubrication and maintenance of joint homeostasis in the temporomandibular joint (TMJ). However, the clinical evidence regarding synovial fluid (SF) lubricin levels remains limited and fragmented. This scoping review aimed to map and synthesize the available clinical evidence on lubricin levels in patients with temporomandibular disorders (TMDs) and their relationship to clinical outcomes, particularly pain and mandibular mobility. Searches were conducted in PubMed, Scopus, ACM, BASE, Cochrane, ClinicalTrials.gov, and Google Scholar. After duplicate removal and screening, two studies were included in the final synthesis. Preliminary findings from these studies suggest that (SF) lubricin levels may be lower in more advanced TMJ pathology, particularly in degenerative disease. Earlier stages of internal derangement showed lubricin concentrations closer to those observed in healthy controls, whereas advanced internal derangement and osteoarthritic disease were potentially associated with lower levels. One study also reported an inverse correlation between lubricin concentration and pain intensity, while the other demonstrated impaired boundary lubrication in TMD groups. Overall, the available clinical evidence is very limited and insufficient to establish PRG4 as a validated biomarker but suggests a possible association between reduced SF lubricin levels and more advanced TMJ disease. Further well-designed clinical studies are required to confirm these observations and clarify their diagnostic and therapeutic relevance. Full article

Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial degenerative disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation, leading to pain and functional impairment in affected individuals. Despite its clinical impact, effective disease-modifying treatments remain limited, highlighting the need for innovative therapeutic approaches for treating this condition in the future. This manuscript examines the biological rationale, clinical applications, and therapeutic potential of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) in the management of TMJ-OA. As autologous platelet-derived biomaterials, PRP and i-PRF contain high concentrations of growth factors and bioactive molecules that can modulate inflammatory responses and support tissue repair. PRP is associated with a relatively rapid release of these mediators, whereas i-PRF forms a fibrin matrix that may enable a more sustained release profile. Current clinical evidence suggests that both therapies show potential to contribute to pain reduction and may facilitate improvements in mandibular function. However, substantial heterogeneity in preparation protocols, study designs, and outcome measures limits the comparability and generalizability of these findings to the general population. Overall, PRP and i-PRF represent promising, minimally invasive regenerative strategies for managing TMJ-OA. Full article

Computed tomography (CT) is used to support the diagnosis of equine temporomandibular joint (TMJ) disease; however, its diagnostic accuracy remains unclear. This study aimed to evaluate the relationship between CT findings and histopathological manifestations of osteoarthritis (OA) in equine TMJs. A total of 82 TMJs were CT-imaged, sampled, grouped into age-related and OA-related groups, and analyzed for frequency distributions, correlations, and CT-based TMJ OA diagnosis. CT findings were observed in 79% of joints, including ‘CT anatomical variations’ considering to reflect age-related remodeling. Only 50% of joints showed co-occurrence of CT findings and histopathological manifestations of OA, confirming that not all CT findings are indicative of disease. Including all CT findings in the CT-based diagnosis of TMJ OA yielded a specificity of 0.41 (95% CI: 0.26–0.58), suggesting a high rate of false-positive diagnoses. Excluding all ‘CT anatomical variations’ resulted in a sensitivity of 0.56 (95% CI: 0.40–0.72), indicating a substantial number of false-negative diagnoses. However, inclusion of specific ‘CT anatomical variation’—subchondral bone cysts—into the studied CT-based diagnosis increased sensitivity to 0.79 (95% CI: 0.62 to 0.89) while maintaining high specificity of 0.92 (95% CI: 0.80–0.98). Including this subset of CT findings in the diagnosis of equine TMJ OA may improve the accuracy of disease detection; however, the clinical relevance of the present cadaver investigation needs to be confirmed in in vivo studies. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative maxillofacial disorder marked by progressive cartilage degradation and subchondral bone resorption, severely compromising patients’ quality of life. Intra-articular injection (IA), a standard route for conservative therapy, offers clinical advantages in safety and efficacy; however, outcomes remain limited due to short drug retention, poor tissue penetration, and variable agent efficacy, necessitating repeated administration. To overcome these limitations, fisetin-loaded poly (lactic-co-glycolic acid) nanoparticles (FST-PNP) were developed as a localized drug delivery system (DDS) for TMJOA treatment. Physicochemical analyses showed FST-PNP had uniform spherical morphology, excellent dispersibility, stability, high encapsulation efficiency, and substantial drug loading capacity. An in vitro study demonstrated more sustained and stable release from FST-PNP than free fisetin. The in vivo IA administration of FST-PNP preserved mandibular condylar osteochondral structures in TMJOA models. Notably, FST-PNP suppressed the expression of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) as catabolic enzymes and downregulated p16 and p21 as senescence markers, indicating synergistic anti-inflammatory and anti-senescent effects. These findings highlight FST-PNP as a DDS integrating controlled-release with multifaceted therapeutic actions, providing a promising strategy for IA therapy of TMJOA. Full article

Background: Magnetic resonance imaging (MRI) is the reference standard for evaluating temporomandibular joint (TMJ) disorders, particularly for assessing disc position, joint effusion, and degenerative changes. With increasing imaging demands and advances in deep learning, artificial intelligence (AI) has emerged as a potential adjunct to expert interpretation. This systematic review aimed to compare the diagnostic performance of AI-based models with that of human experts in TMJ MRI analysis. Methods: This review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251174127). A systematic search of PubMed/MEDLINE, ScienceDirect, Wiley Online Library, and Springer Nature Link was performed for studies published between 2020 and 2026. Eligible studies included human participants undergoing TMJ MRI and evaluated AI, machine learning, or deep learning models against human expert interpretation. Extracted outcomes included sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC), and agreement metrics. Risk of bias was assessed using QUADAS-2. Due to substantial heterogeneity, a narrative synthesis was conducted. Results: Five retrospective diagnostic accuracy studies were included, comprising sample sizes ranging from 118 to 1474 patients. Target conditions included anterior disc displacement, joint effusion, osteoarthritis, and disc perforation. AI models demonstrated strong discriminative performance, with reported AUC values ranging from 0.79 to 0.98. In direct comparisons, AI achieved diagnostic accuracy comparable to experienced radiologists. AI systems frequently demonstrated higher specificity and similar overall accuracy, whereas human experts often showed higher sensitivity. In osteoarthritis assessment, AI performance approached expert level and exceeded that of less experienced readers. All studies were retrospective and predominantly single-center, with heterogeneous reference standards and limited external validation. Conclusions: AI achieves diagnostic performance comparable to experienced clinicians in TMJ MRI interpretation and shows promise as a decision-support tool. Nevertheless, it should be regarded as complementary to, rather than a replacement for, expert radiological assessment pending further rigorous validation. Full article

Temporomandibular disorders (TMDs) are multifactorial conditions traditionally attributed to excessive mechanical loading on the temporomandibular joint, leading to clinical manifestations ranging from joint sounds to structural deformation. Contributing factors include trauma, occlusal abnormalities, psychological stress, and bruxism. However, immune and molecular alterations associated with early disease activity are not systematically integrated into structure-centered TMD frameworks. Emerging evidence indicates that temporomandibular joint osteoarthritis (TMJOA) involves activation of innate immunity caused by damage-associated molecular patterns (DAMPs) generated through mechanical loading, together with non-antigen-specific adaptive immune responses, including macrophage polarization and T helper 17 (Th17) and regulatory T (Treg) cell imbalance. Inflammatory and mechanical inputs converge through shared signaling modules and mechanoresponsive transcriptional programs, promoting extracellular matrix degradation, fibrotic remodeling, and subchondral bone remodeling. This review synthesizes the current immunopathological and mechanobiological evidence and introduces temporomandibular immunologic disease (TMID) as a mechanism-oriented framework, characterized by a reinforcing cycle between mechanically induced tissue damage and immune activation within the temporomandibular joint (TMJ) microenvironment. TMID complements TMJOA and Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) structural diagnostic categories while excluding antigen-specific autoimmune arthritides such as rheumatoid arthritis, thus functioning as a mechanistic overlay framework for the integration of immuno-mechanical signaling networks in immune-active, mechanically driven TMJ pathology. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage destruction, and chondrocyte apoptosis plays a critical role in TMJOA progression. As chondrocytes reside in an avascular microenvironment inside the cartilage matrix, energy production via glycolysis is crucial for their survival. This study investigated the role of the key glycolytic enzyme Hexokinase 2 (HK2) in TMJOA pathogenesis and the therapeutic potential of dental pulp stem cell-derived extracellular vesicles (DPSC-EVs). In a rat experimental TMJOA model induced by monosodium iodoacetate (MIA) intra-articular injection, we observed a significantly decreased expression of HK2 along with cartilage matrix degradation. In the in vitro study, MIA induced chondrocyte apoptosis with caspase-3 activation, accompanied by impaired glycolytic function. Intervention with DPSC-EVs effectively rescued the expression of HK2 within chondrocytes, leading to a notable restoration of cellular glycolysis. Consequently, DPSC-EV treatment markedly attenuated the progression of TMJOA by reducing chondrocyte apoptosis and improved cartilage integrity. Our findings demonstrated that DPSC-EVs represent a promising cell-free therapeutic strategy for TMJOA, exerting their protective effects by targeting HK2, thereby preserving chondrocyte viability and attenuating osteoarthritis development. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration and subchondral bone remodeling, resulting in chronic pain and functional impairment. Although conservative treatments such as physical therapy and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used, their effectiveness is limited due to the poorly understood pathophysiology of TMJOA. Identifying reliable molecular biomarkers is essential to improving early diagnosis and guiding therapeutic development. This proof-of-concept study aims to identify candidate salivary biomarkers for TMJOA using an integrative approach combining clinical validation with in silico analysis. RNA sequencing was performed on saliva samples from TMJOA patients and healthy controls. In parallel, publicly available transcriptomic dataset GSE205389 was analyzed to identify differentially expressed genes (DEGs). DEGs were validated using qRT-PCR. Gene set enrichment analysis (GSEA) and Metascape were used to explore biological pathways associated with TMJOA. Integration of clinical and in silico RNA sequencing datasets identified 2758 and 3548 DEGs, respectively, with 743 overlapping genes. Pathway enrichment analyses highlighted immune-related, metabolic and osteoclast-related pathways. Four genes, CRIP1, PPA1 and TARS1 (statistically significant) and GCLC (non-significant trend), were validated by qRT-PCR in the clinical saliva samples, confirming elevated expression in TMJOA patients. Validation of the in silico dataset showed an upregulation of PTK2B, ABL1, TNF and IL-1B, supporting their relevance as salivary biomarkers in TMJOA. This exploratory study identifies four candidate salivary genes, CRIP1, PPA1, TARS1 and GCLC, as candidate salivary biomarkers for TMJOA, offering insights into disease mechanisms. Larger studies are needed to validate these findings and assess their clinical utility. Full article