Osteoarthritis Therapy Research Articles

Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study

ObjectiveTo identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with US imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA). DesignIn the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared ultrasound (US) measures of synovitis (n=118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression, while controlling for covariates. ResultsHistopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (OR=1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (-1.47 [95%CI -2.88, -0.05]), even while adjusting for synovial inflammation (-1.61 [95%CI -3.12, -0.10]). ConclusionsSynovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.

A Reactive Oxygen Species "Sweeper" Based on Hollow Mesopore Cerium Oxide Nanospheres for Targeted and Anti-Inflammatory Management of Osteoarthritis.

Osteoarthritis (OA) is a progressive joint disorder characterized by sustained oxidative stress, chronic inflammation, and the degradation of cartilage. Despite extensive research on nanocarrier treatment strategies, the therapeutic efficacy remains limited due to the lack of satisfactory vehicles that can simultaneously exhibit excellent ROS scavenging capabilities and high drug loading capacity for effective nonsurgical management of OA. In this work, we propose an innovative strategy utilizing hollow mesoporous cerium oxide nanospheres coated with membranes derived from apoptotic chondrocytes as a reactive oxygen species "sweeper" for targeted and anti-inflammatory therapy of OA. The developed DEX@HMCeNs@M demonstrates superior drug loading capacity, notable antioxidant properties, favorable biocompatibility, and controlled drug release. By leveraging the camouflage provided by apoptotic chondrocyte membranes, the engineered DEX@HMCeNs@M, which bear natural "eat me" signals, can effectively mimic chondrocyte apoptotic bodies within the joints, thereby enabling targeted delivery of the anti-inflammatory drug DEX and subsequent controlled release triggered by the acidic environment of OA. Both in vitro and in vivo experiments validate the enhanced therapeutic efficacy of our DEX@HMCeNs@M sweeper, which operates through a synergistic mechanism involving scavenging of ROS overproduction, inhibition of inflammation, restoration of mitochondrial damage, and reduction of chondrocyte apoptosis. These findings underscore the potential and efficiency of our developed DEX@HMCeNs@M strategy as an encouraging interventional approach for the progressive treatment of OA.

Identity of the pathogenesis, genetic and epigenetic mechanisms of osteoarthritis and rheumatoid arthritis development

Osteoarthritis is characterized by heterogeneity of clinical manifestations and, in some cases, a severe progressive course. In this regard, it is important to identify new molecular targets for the treatment of the disease. To determine the role of autoimmune processes, general genetic and epigenetic changes in osteoarthritis and rheumatoid arthritis, as well as to identify osteoarthritis-specific ribonucleic acids (microRNAs), potential targets for targeted therapy, information was searched using scientific platforms PubMed, Scopus, ResearchGate, RSCI over the past 10 years. Although the pathogenesis of rheumatoid arthritis and osteoarthritis differs, evidence has been obtained that identical pathological immune reactions are involved in the mechanism of osteoarthritis and disruption of the expression of 26 identical genes with identical changes in the levels of 13 of them. Changes in the expression of the same microRNAs (miR-140, miR-149, miR-25, miR-146a, miR-16, miR-23b) were detected in osteoarthritis and rheumatoid arthritis. Molecular genetic studies make it possible to find new markers of pathological immune reactions in osteoarthritis, which can be used to treat the disease and prevent its rapid progression, as well as to design targeted therapy using gene expression products as targets. MicroRNAs associated with osteoarthritis and rheumatoid arthritis and involved in the pathogenesis of both diseases may become promising targets for targeted therapy of osteoarthritis and rheumatoid arthritis.

Effects of human umbilical cord mesenchymal stem cell-derived exosomes in the rat osteoarthritis models.

Mesenchymal stem cells (MSCs) offer great potential for treatment of osteoarthritis (OA) by promoting articular cartilage regeneration via paracrine secretion of exosomes; however, the underlying mechanisms are not fully understood. This study aimed to explore the therapeutic effects of exosomes secreted by human umbilical cord-derived MSCs (hUC-MSCs) in rat models of OA and reveal the underlying mechanisms. UC-MSCs and UC-MSC-exosomes were prepared and identified by transmission electron microscopy and flow cytometry. IL-1β-induced OA chondrocytes and the operation and collagenase-induced OA rat models were established. The results of micro-computed tomography, histology, and immunohistochemistry showed that UC-MSC-exosomes promoted cartilage regeneration in OA rats. ELISA results showed that the levels of synovial fluid cytokines, TNF-α, IL-1β, and IL-6, were lower in exosome therapy group than control group in both OA rat models. Exosome treatment significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1β, and upregulated collagen II expression. These findings suggest that hUC-MSC-exosomes offer a promising option for the therapy for OA.

Локальная терапия при остеоартрите и патологиях околосуставных мягких тканей: фокус на гиалуроновую кислоту

Локальная терапия при остеоартрите и патологиях околосуставных мягких тканей: фокус на гиалуроновую кислоту

Hypoxia-responsive microgels act as an intra-articular lubricant and inflammatory inhibitor for osteoarthritis therapy

The reduced oxygen concentration is a distinctive feature of osteoarthritic (OA) cartilage, whereas the mechanical friction also contributes to the inflammatory hypoxia microenvironment of OA. Herein, novel hypoxia-responsive methylprednisolone (MP) delivery microgels combining the capability of reactive oxygen species (ROS)-depletion and lubrication were constructed for regulating the microenvironment of OA. Methacrylate-modified sulfonated azocalix[4] arene (MACA) loaded with MP, the copolymers consisting of bioinspired lubricant 2-methacryloxyethyl phosphorylcholine (MPC), and polyethylene glycol-modified ROS-responsive poly(thioketal) (PEG-4PTK) were crosslinked together to construct the microgels. The zwitterionic MPC offered a lubrication effect, while the ROS-elimination was contributed by the PTK segments and the phenol groups in MACA. The microgels responsively released cargos in inflammatory environment and decreased inflammation by inhibiting the production of ROS and regulating the expression of inflammatory cytokines, and showed the lowest hypoxia-inducible factor-1α (HIF-1α) positive area and presented more deposition of glycosaminoglycans and collagen II with a smoother and integrated cartilage structure in therapy of OA in rats in vivo.

CRISPR-mediated Sox9 activation and RelA inhibition enhance cell therapy for osteoarthritis

Osteoarthritis (OA) is a painful and debilitating disease affecting over 500 million people worldwide. Intraarticular injection of mesenchymal stromal cells (MSCs) shows promise for the clinical treatment of OA, but the lack of consistency in MSC preparation and application makes it difficult to further optimize MSC therapy and to properly evaluate the clinical outcomes. In this study, we used Sox9 activation and RelA inhibition, both mediated by the CRISPR-dCas9 technology simultaneously, to engineer MSCs with enhanced chondrogenic potential and downregulated inflammatory responses. We found that both Sox9 and RelA could be fine-tuned to the desired levels, which enhances the chondrogenic and immunomodulatory potentials of the cells. Intraarticular injection of modified cells significantly attenuated cartilage degradation and palliated OA pain compared with the injection of cell culture medium or unmodified cells. Mechanistically, the modified cells promoted the expression of factors beneficial to cartilage integrity, inhibited the production of catabolic enzymes in osteoarthritic joints, and suppressed immune cells. Interestingly, a substantial number of modified cells could survive in the cartilaginous tissues including articular cartilage and meniscus. Together, our results suggest that CRISPR-dCas9-based gene regulation is useful for optimizing MSC therapy for OA.

Metformin as adjuvant therapy in obese knee osteoarthritis patients

AimsThis study aimed at investigating the efficacy of metformin as adjuvant therapy for obese knee osteoarthritis (OA) patients, considering its anti-inflammatory and cartilage-protective effects.Patients and methodsIn this randomized, double-blind, placebo-controlled study, 50 obese knee OA patients were assigned randomly to two groups, the metformin group (n = 25) which was treated with metformin 500 mg orally BID plus celecoxib 200 mg orally once daily, and the placebo group (n = 25) which was treated with placebo tablets BID plus celecoxib 200 mg orally once daily for 12 weeks. Cartilage Oligomeric Matrix Protein (COMP), C-terminal cross-linked telopeptide of type I collagen (CTX-1), and Interleukin 1-beta (IL-1β) serum levels were measured, while Western Ontario and McMaster Universities Arthritis Index (WOMAC) score assessed knee pain, stiffness, and physical function at baseline and after 12 weeks.ResultsFollowing a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1β in the serum compared to the placebo group (p = 0.0081, p = 0.0106, and p = 0.0223, respectively). Furthermore, metformin group produced significant improvements in WOMAC total scale (p < 0.0001), specifically in knee pain, stiffness, and physical function compared to placebo group (p < 0.0001, p < 0.0001, and p < 0.0001, respectively).ConclusionMetformin as an adjuvant therapy in obese knee OA patients may have beneficial effects on cartilage degradation and inflammation, as evidenced by the significant decreases in serum COMP, CTX-1, and IL-1β levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores.Clinicaltrials.gov IDNCT05638893/Registered December 6, 2022 — Retrospectively.

Donor Sites and Harvesting Techniques Affect miRNA Cargos of Extracellular Vesicles Released by Human Adipose-Derived Mesenchymal Stromal Cells.

Osteoarthritis (OA) is a degenerative joint disorder characterized by the progressive deterioration of articular cartilage driven and sustained by catabolic and inflammatory processes that lead to pain and functional impairment. Adipose-derived stem cells (ASCs) have emerged as a promising therapeutic strategy for OA due to their regenerative potential, which mainly relies on the adaptive release of paracrine molecules that are soluble or encapsulated in extracellular vesicles (EVs). The biological effects of EVs specifically depend on their cargo; in particular, microRNAs (miRNAs) can specifically modulate target cell function through gene expression regulation. This study aimed to investigate the impact of collection site (abdominal vs. peri-trochanteric adipose tissue) and collection method (surgical excision vs. lipoaspiration) on the miRNAs profile in ASC-derived EVs and their potential implications for OA therapy. EV-miRNA cargo profiles from ASCs of different origins were compared. An extensive bioinformatics search through experimentally validated and OA-related targets, pathways, and tissues was conducted. Several miRNAs involved in the restoration of cartilage homeostasis and in immunomodulation were identified in all ASC types. However, EV-miRNA expression profiles were affected by both the tissue-harvesting site and procedure, leading to peculiar characteristics for each type. Our results suggest that adipose-tissue-harvesting techniques and the anatomical site of origin influence the therapeutic efficacy of ASC-EVs for tissue-specific regenerative therapies in OA, which warrants further investigation.

Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy.

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements thatcontain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.

The Efficacy of Bone Marrow Stem Cell Therapy in Hip Osteoarthritis: A Scoping Review

Background: Hip osteoarthritis (HOA) is a prevalent degenerative joint disease with various treatment approaches. Biological agents, such as bone-marrow derived stem cells (BM-MSC) therapy, have recently been proposed as a treatment option in the management of HOA. Purpose: We sought to further analyze the use of BM-MSC therapy by investigating the following questions. What is the standard preparation and practice? Does a dose response exist between stem cell therapy and clinical outcome? Does BM-MSC therapy alone produce effective clinical outcomes? Methods: We conducted a scoping review using the Methodological Expectations of Cochrane Intervention Reviews Manual and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for scoping reviews. A comprehensive search of PubMed, Embase, Cochrane CENTRAL, Scopus, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Core Collection was performed in June 2023 of studies using exclusively BM-MSC injections for the treatment of HOA. Study characteristic, injection preparation and dosage, clinical outcome measures, and adverse effect data were extracted and interpreted by 3 reviewers. Results: Seven studies with a total of 72 patients met the inclusion criteria. Clinical outcome following intra-articular injection of BM-MSCs was measured using the numerical pain scale, the Western Ontario and McMaster Universities Osteoarthritis Index, the visual analogue scale, and other scores, all of which showed reduction in pain and increase in functional ability across studies. Conclusions: This scoping review found that the efficacy of BM-MSC therapy alone in the treatment of HOA appeared beneficial, improving clinical outcomes in each study. All 7 studies used “low-dose” injections with variable follow-up times; thus, a clear dose–response relationship cannot be drawn. Future studies using high doses and analyzing long-term effects of BM-MSC injections in HOA are needed.

Vitamin B6 alleviates osteoarthritis by suppressing inflammation and apoptosis

BackgroundAlthough various anti-inflammatory medicines are widely recommended for osteoarthritis (OA) treatment, no significantly clinical effect has been observed. This study aims to examine the effects of vitamin B6, a component that has been reported to be capable of alleviating inflammation and cell death in various diseases, on cartilage degeneration in OA.MethodsCollagen-induced arthritis (CIA) mice model were established and the severity of OA in cartilage was determined using the Osteoarthritis Research Society International (OARSI) scoring system. The mRNA and protein levels of indicators associated with extracellular matrix (ECM) metabolism, apoptosis and inflammation were detected. The effect of vitamin B6 (VB6) on the mice were assessed using HE staining and masson staining. The apoptosis rate of cells was assessed using TdT-mediated dUTP nick end labeling.ResultsOur results showed a trend of improved OARSI score in mice treated with VB6, which remarkably inhibited the hyaline cartilage thickness, chondrocyte disordering, and knees hypertrophy. Moreover, the VB6 supplementation reduced the protein expression of pro-apoptosis indicators, including Bax and cleaved caspase-3 and raised the expression level of anti-apoptosis marker Bcl-2. Importantly, VB6 improved ECM metabolism in both in vivo and in vitro experiments.ConclusionsThis study demonstrated that VB6 alleviates OA through regulating ECM metabolism, inflammation and apoptosis in chondrocytes and CIA mice. The findings in this study provide a theoretical basis for targeted therapy of OA, and further lay the theoretical foundation for studies of mechanisms of VB6 in treating OA.

SiRNA therapy in osteoarthritis: targeting cellular pathways for advanced treatment approaches.

Osteoarthritis (OA) is a common joint disorder characterized by the degeneration of cartilage and inflammation, affecting millions worldwide. The disease's complex pathogenesis involves various cell types, such as chondrocytes, synovial cells, osteoblasts, and immune cells, contributing to the intricate interplay of factors leading to tissue degradation and pain. RNA interference (RNAi) therapy, particularly through the use of small interfering RNA (siRNA), emerges as a promising avenue for OA treatment due to its capacity for specific gene silencing. siRNA molecules can modulate post-transcriptional gene expression, targeting key pathways involved in cellular proliferation, apoptosis, senescence, autophagy, biomolecule secretion, inflammation, and bone remodeling. This review delves into the mechanisms by which siRNA targets various cell populations within the OA milieu, offering a comprehensive overview of the potential therapeutic benefits and challenges in clinical application. By summarizing the current advancements in siRNA delivery systems and therapeutic targets, we provide a solid theoretical foundation for the future development of novel siRNA-based strategies for OA diagnosis and treatment, paving the way for innovative and more effective approaches to managing this debilitating disease.

IL-1ra gene therapy in equine osteoarthritis improves physiological, anatomical, and biological outcomes of joint degeneration.

To evaluate the effects of a gene transfer approach to IL-1β inhibition in an equine osteochondral chip fragment model of joint injury using a self-complementary adeno-associated virus with interleukin receptor antagonist transgene cassette (scAAVIL-1ra), as posttraumatic osteoarthritis in horses, similar to people, is a significant clinical problem. 16 horses were utilized for the study. All horses had an osteochondral chip fragment induced arthroscopically in one middle carpal joint while the contralateral joint was sham operated. Eight horses received either scAAVIL-1ra or saline in the osteoarthritis joint. Horses were evaluated over 70 days clinically (lameness, imaging, and biomarker analysis) and euthanized at 70 days and evaluated grossly, with imaging and histopathology. The following findings were statistically significant. Injection of scAAVIL-1ra resulted in high synovial fluid levels of IL-1ra (0.5 to 9 μg/mL) throughout the duration of the experiment (70 days). Over the duration, we observed scAAVIL-1ra to improve lameness (lameness score relative improvement of 1.2 on a scale of 0 to 5), cause suppression of prostaglandin E2 (a relative decline of 30 pg/mL), and result in histological improvement in articular cartilage (decreased chondrocyte loss and chondrone formation) and subchondral bone (less osteochondral splitting and osteochondral lesions). Within the synovial membrane of scAAVIL-1ra-treated joints, we also observed perivascular infiltration with CD3-positive WBCs, suggesting lymphocytic T-cell perivascular infiltration commonly observed with viral transduction. These data provide support for further evaluation and optimization of scAAVIL-1ra gene therapy to treat equine osteoarthritis.

Serum ARGS-aggrecan in a phase 2 clinical trial targeting osteoarthritis

OBJECTIVETo monitor serum concentrations of the aggrecan ARGS neoepitope in a clinical trial of ADAMTS-5 inhibition as disease-modifying therapy of knee osteoarthritis, and to investigate relationships between reduction in ARGS and change in cartilage thickness, knee related pain and function. DESIGNROCCELLA trial participants received once-daily oral S201086 75, 150 or 300 mg, or placebo, for 52 weeks. Serum was collected at baseline, 4, 12, 28 and 52 weeks, and 2 weeks post treatment with ARGS measured by an in-house immunoassay. Change from baseline to week 52 in central medial femorotibial compartment cartilage thickness was measured by MRI, function and pain by WOMAC subscores. Associations between cumulative change in ARGS and change in cartilage thickness or WOMAC subscores were evaluated by linear regression. RESULTSS201086 reduced serum levels of ARGS in a dose-dependent manner throughout the treatment period. Maximal reduction was at 4 weeks with a 58.5% [95% CI 60.8%, 56.2%] reduction of ARGS compared to baseline for 300 mg S201086. Two weeks post treatment, ARGS concentrations rebounded with a dose-dependent overshoot compared to baseline levels. Cumulative change of ARGS concentration from baseline to week 52 had no effect on change in cartilage thickness (slope -0.8x10-6 [-2.9x10-6, 1.3x10-6]) or change in WOMAC pain and function (slopes -30x10-6 [-64x10-6, 5.2x10-6] and -97x10-6 [-214x10-6, 20x10-6], respectively) at week 52. CONCLUSIONSystemic inhibition of ADAMTS-5 resulted in markedly reduced serum ARGS, but change in serum ARGS concentrations showed no association with the progression of cartilage thinning, or patient reported pain and function. ClinicalTrials.govNCT03595618.

Consensus on clinical drug therapy for knee osteoarthritis in China (2023)

Osteoarthritis (OA) is a heterogeneous disease that involves structural alterations in the articular cartilage, synovium, ligaments, subchondral bone, and the surrounding bone tissue. Among the various types of OA, knee osteoarthritis (KOA) is the most prevalent, presenting with symptoms such as joint pain, swelling, stiffness, and functional limitations. And its high disability rate places a significant burden on both individuals and society. Pharmacological intervention plays a crucial role in the comprehensive management of KOA. However, the establishment of standardized treatment protocols for the accurate and appropriate selection of medications for patients remain pressing clinical challenges. The Osteoarthritis Group of the Rheumatology and Immunology Physicians Branch of the Chinese Medical Doctor Association has developed this expert consensus by drawing upon current research findings, relevant guidelines, and consensus statements from both domestic and international sources. This consensus adheres to international standards for consensus development and incorporates input from a diverse panel of experts.The consensus encompasses six aspects: disease prevention, treatment goals, clinical typing, therapeutic drugs, follow-up and evaluation, and medication for comorbid populations. A total of 27 recommendations are put forward, aiming to provide clinicians with guidance for the safe and standardized use of drugs, thereby improving the diagnosis and treatment level of KOA and benefiting patients.

Aromatic Plants as Potential Resources to Combat Osteoarthritis.

Osteoarthritis, which affects an estimated 10% of men and 18% of women over the age of 60 and is increasing in genetic prevalence and incidence, is acknowledged as the condition that degrades the quality of life for older adults in the world. There is currently no known treatment for osteoarthritis. The majority of therapeutic methods slow the progression of arthritis or treat its symptoms, making effective treatment to end the degenerative process of arthritis elusive. When non-pharmacological therapy is ineffective, various pharmacological therapies may be used to treat osteoarthritis. Pharmacological therapy, however, can have major adverse effects and be very expensive. As a result, alternative remedies have been researched. The promise for the safe and efficient management of osteoarthritis has been demonstrated by herbal remedies. Experimental research suggests that herbal extracts and compounds can reduce inflammation, inhibit catabolic processes, and promote anabolic processes that are important for treating osteoarthritis. Due to their therapeutic and innate pharmacological qualities, aromatic herbs are frequently employed as herbal remedies. Recent research has shown that aromatic plants have the potency to treat osteoarthritis. Additionally, complex mixtures of essential oils and their bioactive ingredients, which have anti-inflammatory and antioxidant properties and are obtained from aromatic plants, are frequently utilized as complementary therapies for osteoarthritis. To establish new study avenues, the advantageous anti-osteoarthritic effects of aromatic herbal medicines, including plants, essential oils, and their bioactive components, are extensively discussed.

Injectable dECM-enhanced hyaluronic microgels with spatiotemporal release of cartilage-specific molecules to improve osteoarthritic chondrocyte’s function

The interior environment of articular cartilage in osteoarthritis (OA) presents substantial hurdles, leading to the malfunction of chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix. Despite this, most clinical treatments primarily provide temporary relief from OA discomfort without arresting OA progression. This study aimed to alleviate OA by developing intra-articular injectable dECM-enhanced hyaluronic (HE) microgels. The HE hydrogel was engineered and shaped into uniformly sized microgels using microfluidics and photopolymerization techniques. These microgels provided a spatiotemporal cascade effect, facilitating the rapid release of growth factors and a slower release of ECM macromolecules and proteins. This process assisted in the recovery of OA chondrocytes’ function, promoting cell proliferation, matrix synthesis, and cartilage-specific gene expression in vitro. It also effectively aided repair of the collagen II-enriched hyaline cartilage and significantly reduced the severity of OA, as demonstrated by radiological observation, gross appearance, histological/immunohistochemical staining, and analysis in an OA rat model in vivo. Collectively, the HE injectable microgels with spatiotemporal release of cartilage-specific molecules have shown promise as a potential candidate for a cell-free OA therapy approach.Graphical

A multifunctional nanofluorescent drug carrier constructed from a Ho(III) complex for treatment of Osteoarthritis

Osteoarthritis (OA) is a chronic disease affecting joints and bones. Current treatment mainly involves non-steroidal anti-inflammatory drugs (NSAIDs). Developing effective drug delivery systems is crucial for future OA therapy. We synthesized a novel Ho(III) coordination polymer, denoted as [Ho(bta)0.5(ox)0.5(H2O)2]·2H2O (1), via hydrothermal reaction of Ho(NO3)3·6H2O with oxalic acid (H2ox) and 1,2,4,5-benzenetetracarboxylic acid (H4bta) ligands. Fluorescence spectroscopy demonstrated excellent blue fluorescence emission of complex 1 (CIE standard coordinates: (0.1421, 0.1148)), suggesting its potential as a novel fluorescent material for applications such as anti-counterfeiting, sensing, and fluorescence labeling. Utilizing biocompatible and anti-inflammatory hydroxyapatite (HA) and cholesterol (CHOL), we successfully synthesized amphiphilic polymer HA-CHOL and applied it for encapsulating 1@NSAIDs to prepare HA-CHOL-1@NSAIDs. To evaluate the therapeutic potential of this new system for OA, we established an in vitro cell model and assessed the impact of HA-CHOL-1@NSAIDs on OA progression. Molecular docking simulations suggested potential binding interactions between carboxyl groups on complex 1 and receptor proteins, with multiple hydrogen bonds formed, indicating strong interactions.

A Narrative Review of the Roles of Chondromodulin-I (Cnmd) in Adult Cartilage Tissue.

Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte proliferation, cartilage homeostasis, and the blocking of angiogenesis. In vivo and in vitro studies on Cnmd, also suggest an involvement in bone repair and in delaying OA progression. Its downregulation correlates with OA severity, indicating its potential as a therapeutic target. Further research is needed to fully understand the mode of action of Cnmd and its beneficial implications for managing OA. This comprehensive review aims to elucidate the molecular characteristics of Cnmd, from its expression pattern, role in cartilage maintenance, callus formation during bone repair and association with OA.