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1.
Phytomedicine ; 129: 155593, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38621329

ABSTRACT

BACKGROUND: Preventing joint edema is crucial in halting osteoarthritis (OA) progression. Growing clinical evidence indicate that Jianpi-Tongluo Formula (JTF) may have a promising anti-edema effect. However, the therapeutic properties of JTF and the underlying mechanisms remains unclear. MATERIALS AND METHODS: An OA rat model was established and employed to evaluate pharmacological effects of JTF in vivo based on dynamic histopathologic assessments and micro-CT observations. Then, OA-related genes and potential targets of JTF were identified through clinical transcriptomic data analysis and "disease gene-drug target" network analysis, which were verified by a series of in vivo experiments. RESULTS: JTF administration effectively reduced pain and joint edema, inhibited matrix degradation, chondrocyte apoptosis, and aquaporin expression in OA rats. Notably, JTF dose-dependently reversed damage-associated molecular patterns and inflammatory factor upregulation. Mechanically, our "disease gene-drug target" network analysis indicated that the NCOA4-HMGB1-GSK3B-AQPs axis, implicated in ferroptosis and aquaporin dysregulation, may be potentially served as a target of JTF against OA. Accordingly, JTF mitigated NCOA4, HMGB1, and GSK3B expression, oxidative stress, and iron metabolism aberrations in OA rats. Furthermore, JTF treatment significantly attenuated the aberrant upregulation of AQP1, AQP3, and AQP4 proteins observed in cartilage tissues of OA rats. CONCLUSION: Our data reveal for the first time that JTF may exert cartilage protective and anti-edema effects in osteoarthritis therapy by inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.


Subject(s)
Ferroptosis , HMGB1 Protein , Osteoarthritis , Rats, Sprague-Dawley , Animals , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Ferroptosis/drug effects , Rats , Male , HMGB1 Protein/metabolism , Drugs, Chinese Herbal/pharmacology , Edema/drug therapy , Aquaporins/metabolism , Nuclear Receptor Coactivators/metabolism , Disease Models, Animal , Aquaporin 3/metabolism , Aquaporin 1/metabolism
2.
Undersea Hyperb Med ; 51(1): 53-58, 2024.
Article in English | MEDLINE | ID: mdl-38615354

ABSTRACT

We present two cases of cricoid chondronecrosis treated with hyperbaric oxygen (HBO2) therapy. Both patients presented with biphasic stridor and dyspnea several weeks after an intubation event. Tracheostomy was ultimately performed for airway protection, followed by antibiotic treatment and outpatient HBO2 therapy. Both patients were decannulated within six months of presentation and after at least 20 HBO2 therapy sessions. Despite a small sample size, our findings are consistent with data supporting HBO2 therapy's effects on tissue edema, neovascularization, and HBO2 potentiation of antibiotic treatment and leukocyte function. We suggest HBO2 therapy may have accelerated airway decannulation by way of infection resolution as well as the revitalization of upper airway tissues, ultimately renewing the structural integrity of the larynx. When presented with this rare but significant clinical challenge, physicians should be aware of the potential benefits of HBO2 therapy.


Subject(s)
Hyperbaric Oxygenation , Physicians , Humans , Oxygen , Research , Anti-Bacterial Agents
3.
Materials (Basel) ; 17(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38612211

ABSTRACT

The damping system ensured by the osteochondral (OC) unit is essential to deploy the forces generated within load-bearing joints during locomotion, allowing furthermore low-friction sliding motion between bone segments. The OC unit is a multi-layer structure including articular cartilage, as well as subchondral and trabecular bone. The interplay between the OC tissues is essential in maintaining the joint functionality; altered loading patterns can trigger biological processes that could lead to degenerative joint diseases like osteoarthritis. Currently, no effective treatments are available to avoid degeneration beyond tissues' recovery capabilities. A thorough comprehension on the mechanical behaviour of the OC unit is essential to (i) soundly elucidate its overall response to intra-articular loads for developing diagnostic tools capable of detecting non-physiological strain levels, (ii) properly evaluate the efficacy of innovative treatments in restoring physiological strain levels, and (iii) optimize regenerative medicine approaches as potential and less-invasive alternatives to arthroplasty when irreversible damage has occurred. Therefore, the leading aim of this review was to provide an overview of the state-of-the-art-up to 2022-about the mechanical behaviour of the OC unit. A systematic search is performed, according to PRISMA standards, by focusing on studies that experimentally assess the human lower-limb joints' OC tissues. A multi-criteria decision-making method is proposed to quantitatively evaluate eligible studies, in order to highlight only the insights retrieved through sound and robust approaches. This review revealed that studies on human lower limbs are focusing on the knee and articular cartilage, while hip and trabecular bone studies are declining, and the ankle and subchondral bone are poorly investigated. Compression and indentation are the most common experimental techniques studying the mechanical behaviour of the OC tissues, with indentation also being able to provide information at the micro- and nanoscales. While a certain comparability among studies was highlighted, none of the identified testing protocols are currently recognised as standard for any of the OC tissues. The fibril-network-reinforced poro-viscoelastic constitutive model has become common for describing the response of the articular cartilage, while the models describing the mechanical behaviour of mineralised tissues are usually simpler (i.e., linear elastic, elasto-plastic). Most advanced studies have tested and modelled multiple tissues of the same OC unit but have done so individually rather than through integrated approaches. Therefore, efforts should be made in simultaneously evaluating the comprehensive response of the OC unit to intra-articular loads and the interplay between the OC tissues. In this regard, a multidisciplinary approach combining complementary techniques, e.g., full-field imaging, mechanical testing, and computational approaches, should be implemented and validated. Furthermore, the next challenge entails transferring this assessment to a non-invasive approach, allowing its application in vivo, in order to increase its diagnostic and prognostic potential.

4.
Exp Gerontol ; 190: 112413, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38570055

ABSTRACT

BACKGROUND: Osteoporotic osteoarthritis (OP-OA) is a severe pathological form of OA, urgently requiring precise management strategies and more efficient interventions. Emodin (Emo), an effective ingredient found in the traditional Chinese medicine rhubarb, has been dEmonstrated to promote osteogenesis and inhibit extracellular matrix degradation. In this study, we aimed to investigate the interventional effects of Emo on the subchondral bone and cartilage of the knee joints in OP-OA model rats. METHODS: Thirty-two SD rats were randomly and equally divided into sham, OP-OA, Emo low-dose, and Emo high-dose groups. Micro-CT scanning was conducted to examine the bone microstructure of the rat knee joints. H&E and Safranin O and Fast Green staining (SO&FG) were performed for the pathomorphological evaluation of the rat cartilage tissues. ELISA was used to estimate the rat serum expression levels of inflammatory factors, including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Additionally, the CCK-8 assay was utilized for determining the viability of Emo-treated BMSCs. Western blot and real-time PCR analyses were also employed to measure the bone formation indexes and cartilage synthesis and decomposition indexes. Lastly, the osteogenic and chondrogenic differentiation efficiency of the BMSCs was investigated via Alizarin Red and Alcian Blue staining. RESULTS: Emo intervention alleviated the bone microstructural disruption of the subchondral bone and articular cartilage in the OP-OA rats and up-regulated the expression of bone and cartilage anabolic metabolism indicators, decreased the expression of cartilage catabolism indicators, and diminished the expression of inflammatory factors in the rat serum (P<0.05). Furthermore, Emo reversed the decline in the osteogenic and chondrogenic differentiation ability of the BMSCs (P<0.05). CONCLUSION: Emo intervention mitigates bone loss and cartilage damage in OP-OA rats and promotes the osteogenic and chondrogenic differentiation of BMSCs.


Subject(s)
Cartilage, Articular , Emodin , Osteoporosis , Rats, Sprague-Dawley , X-Ray Microtomography , Animals , Emodin/pharmacology , Cartilage, Articular/drug effects , Cartilage, Articular/pathology , Cartilage, Articular/metabolism , Rats , Osteoporosis/drug therapy , Osteoporosis/prevention & control , Female , Disease Models, Animal , Osteogenesis/drug effects , Mesenchymal Stem Cells/drug effects , Tumor Necrosis Factor-alpha/metabolism , Interleukin-1beta/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/pathology
5.
Adv Mater ; 36(27): e2401009, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38548296

ABSTRACT

Tissue engineering and electrotherapy are two promising methods to promote tissue repair. However, their integration remains an underexplored area, because their requirements on devices are usually distinct. Triboelectric nanogenerators (TENGs) have shown great potential to develop self-powered devices. However, due to their susceptibility to moisture, TENGs have to be encapsulated in vivo. Therefore, existing TENGs cannot be employed as tissue engineering scaffolds, which require direct interaction with surrounding cells. Here, the concept of triboelectric scaffolds (TESs) is proposed. Poly(glycerol sebacate), a biodegradable and relatively hydrophobic elastomer, is selected as the matrix of TESs. Each hydrophobic micropore in multi-hierarchical porous TESs efficiently serves as a moisture-resistant working unit of TENGs. Integration of tons of micropores ensures the electrotherapy ability of TESs in vivo without encapsulation. Originally hydrophobic TESs are degraded by surface erosion and transformed into hydrophilic surfaces, facilitating their role as tissue engineering scaffolds. Notably, TESs seeded with chondrocytes obtain dense and large matured cartilages after subcutaneous implantation in nude mice. Importantly, rabbits with osteochondral defects receiving TES implantation show favorable hyaline cartilage regeneration and complete cartilage healing. This work provides a promising electronic biomedical device and will inspire a series of new in vivo applications.


Subject(s)
Decanoates , Hydrophobic and Hydrophilic Interactions , Polymers , Regeneration , Tissue Engineering , Tissue Scaffolds , Tissue Scaffolds/chemistry , Animals , Porosity , Rabbits , Tissue Engineering/methods , Decanoates/chemistry , Polymers/chemistry , Mice , Glycerol/chemistry , Glycerol/analogs & derivatives , Cartilage/physiology , Chondrocytes/cytology , Mice, Nude , Biocompatible Materials/chemistry
6.
Dent J (Basel) ; 12(3)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38534273

ABSTRACT

Mandibular retrognathism occurs by insufficient mandibular growth and causes several issues, such as respiratory difficulty and diminished masticatory function. At present, functional orthodontic appliances are used for stimulating mandibular growth in pediatric cases. However, the effectiveness of functional appliances is not always stable in daily practices. A more effective, reliable, and safer therapeutic method for mandibular growth promotion would be helpful for growing mandibular retrognathism patients. As we previously discovered that nutritional supplementation of myo-inositol in growing mice specifically increases mandibular endochondral growth, we performed preclinical animal experiments in rabbits in this study. Briefly, six-week-old male Japanese white rabbits were fed with or without myo-inositol supplementation in laboratory chow until 25 weeks old, and 3D image analysis using micro CT data and histological examinations was done. Myo-inositol had no systemic effect, such as femur length, though myo-inositol specifically augmented the mandibular growth. Myo-inositol increased the thickness of mandibular condylar cartilage. We discovered that the nutritional supplementation of myo-inositol during the growth period specifically augmented mandibular growth without any systemic influence, even in rabbits. Our results suggest the possibility of clinical use of myo-inositol for augmentation of the mandibular growth in growing mandibular retrognathism patients in the future.

7.
J Ethnopharmacol ; 325: 117887, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38346525

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba, as the most widely available medicinal plant worldwide, has been frequently utilized for treat cardiovascular, cerebrovascular, diabetic and other diseases. Due to its distinct pharmacological effects, it has been broadly applications in pharmaceuticals, health products, dietary supplements, and so on. Ginkgolide C (GC), a prominent extract of Ginkgo biloba, possesses potential in anti-inflammatory and anti-oxidant efficacy. AIMS OF THE STUDY: To determine whether GC mitigated the progressive degeneration of articular cartilage in a Monosodium Iodoacetate (MIA)-induced osteoarthritis (OA) rat model by inhibiting the activation of the NLRP3 inflammasome, and the specific underlying mechanisms. MATERIALS AND METHODS: In vivo, an OA rat model was established by intra-articular injection of MIA. The protective effect of GC (10 mg/kg) on articular cartilage was evaluated. Application of ATDC5 cells to elucidate the mechanism of the protective effect of GC on articular cartilage. Specifically, the expression levels of molecules associated with cartilage ECM degrading enzymes, OS, ERS, and NLRP3 inflammasome activation were analyzed. RESULTS: In vivo, GC ameliorated MIA-induced OA rat joint pain, and exhibited remarkable anti-inflammatory and anti- ECM degradation effects via inhibition of the activation of NLRP3 inflammasome, the release of inflammatory factors, and the expression of matrix-degrading enzymes in cartilage. Mechanically, GC inhibited the activation of NLRP3 inflammasome by restraining ROS-mediated p-IRE1α and activating Nrf2/NQO1 signal path, thereby alleviating OA. The ROS scavenger NAC was as effective as GC in reducing ROS production and inhibiting the activation of NLRP3 inflammasome. CONCLUSIONS: GC have exerted chondroprotective effects by inhibiting the activation of NLRP3 inflammasome.


Subject(s)
Cartilage, Articular , Ginkgolides , Lactones , Osteoarthritis , Rats , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Reactive Oxygen Species/metabolism , Chondrocytes , Endoribonucleases/metabolism , Protein Serine-Threonine Kinases/metabolism , Osteoarthritis/chemically induced , Osteoarthritis/drug therapy , Anti-Inflammatory Agents/adverse effects , Iodoacetic Acid/adverse effects , Iodoacetic Acid/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/metabolism
8.
Biomolecules ; 14(2)2024 Jan 27.
Article in English | MEDLINE | ID: mdl-38397390

ABSTRACT

Natural products with health benefits, nutraceuticals, have shown considerable promise in many studies; however, this potential has yet to translate into widespread clinical use for any condition. Notably, many drugs currently on the market, including the first analgesic aspirin, are derived from plant extracts, emphasizing the historical significance of natural products in drug development. Curcumin and resveratrol, well-studied nutraceuticals, have excellent safety profiles with relatively mild side effects. Their long history of safe use and the natural origins of numerous drugs contrast with the unfavorable reputation associated with nutraceuticals. This review aims to explore the nutraceutical potential for treating pseudoachondroplasia, a rare dwarfing condition, by relating the mechanisms of action of curcumin and resveratrol to molecular pathology. Specifically, we will examine the curcumin and resveratrol mechanisms of action related to endoplasmic reticulum stress, inflammation, oxidative stress, cartilage health, and pain. Additionally, the barriers to the effective use of nutraceuticals will be discussed. These challenges include poor bioavailability, variations in content and purity that lead to inconsistent results in clinical trials, as well as prevailing perceptions among both the public and medical professionals. Addressing these hurdles is crucial to realizing the full therapeutic potential of nutraceuticals in the context of pseudoachondroplasia and other health conditions that might benefit.


Subject(s)
Achondroplasia , Biological Products , Curcumin , Curcumin/pharmacology , Resveratrol/pharmacology , Resveratrol/therapeutic use , Dietary Supplements
9.
Chin J Nat Med ; 22(2): 137-145, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38342566

ABSTRACT

Excessive oxidative stress impairs cartilage matrix metabolism balance, significantly contributing to osteoarthritis (OA) development. Celastrol (CSL), a drug derived from Tripterygium wilfordii, has recognized applications in the treatment of cancer and immune system disorders, yet its antioxidative stress mechanisms in OA remain underexplored. This study aimed to substantiate CSL's chondroprotective effects and unravel its underlying mechanisms. We investigated CSL's impact on chondrocytes under both normal and inflammatory conditions. In vitro, CSL mitigated interleukin (IL)-1ß-induced activation of proteinases and promoted cartilage extracellular matrix (ECM) synthesis. In vivo, intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA mice. Mechanistically, it was found that inhibiting nuclear factor erythroid 2-related factor 2 (NRF2) abrogated CSL-mediated antioxidative functions and exacerbated the progression of OA. This study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2, offering a novel therapeutic avenue for arthritis therapy.


Subject(s)
NF-E2-Related Factor 2 , Osteoarthritis , Mice , Animals , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Osteoarthritis/pathology , Pentacyclic Triterpenes/pharmacology , Pentacyclic Triterpenes/metabolism , Chondrocytes , Interleukin-1beta
10.
Fitoterapia ; 174: 105870, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423225

ABSTRACT

A systematic mechanistic review was performed to determine mechanistic evidence for curcumin on pro-inflammatory matrix metalloproteinases and Osteoarthritis to understand the underlying pathophysiology, and to evaluate available human intervention evidence to inform clinical decision making. The systematic literature search was performed in 3 tranches (reviews, mechanistic, intervention studies) using PubMed, with no date limitations and using specific search terms. 65 out of 393 screened papers were accepted based on detailed inclusion and exclusion criteria. The mechanistic search was divided into three searches and the intervention searches were subdivided into four searches. Curcumin demonstrated significant inhibition of matrix metalloproteinases linked to cartilage degradation in Osteoarthritis through reduced activation of the nuclear factor kappa-B signaling pathway via suppressing phosphorylation of Iκßa and p65 nuclear translocation. Mechanistic evidence implicated matrix metalloproteinases in Osteoarthritis by decreasing Type II collagen, leading to cartilage damage. As a potential nutritional intervention for Osteoarthritis, curcumin could reduce inflammatory markers and improve pain and function scores. The evidence indicates most formulations of turmeric extract and curcumin extract, bio-enhanced and non-bio-enhanced, are effective at improving inflammatory markers and pain and function to a greater or lesser extent. Due to the high heterogeneity of the formulations, dosage, and duration of the studies, further research is needed to fully understand curcumin's potential as a promising non-pharmaceutical intervention for Osteoarthritis. This mechanism review identifies a gap in current research for the mechanism by which Type II collagen is mediated.


Subject(s)
Curcumin , Osteoarthritis , Humans , Curcumin/pharmacology , Curcumin/metabolism , Collagen Type II/metabolism , Collagen Type II/pharmacology , Chondrocytes/metabolism , Molecular Structure , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , NF-kappa B/metabolism , Pain , Matrix Metalloproteinases/metabolism
11.
Comb Chem High Throughput Screen ; 27(15): 2187-2205, 2024.
Article in English | MEDLINE | ID: mdl-38279748

ABSTRACT

Rotator cuff tear is a common injury among middle-aged and elderly people, and it has a great impact on patients' physical and mental health and quality of life. Integrative medicine based on Traditional Chinese Medicine (TCM) has certain advantages in the diagnosis and treatment of rotator cuff tears. TCM, which mainly involves the use of plant-based products, has relatively stable and reliable curative effects. It is of great significance to formulate a combined diagnosis and treatment plan for rotator cuff tear based on evidence-based medicine, which can help to standardize the clinical diagnosis and treatment techniques of TCM and Western medicine and achieve better therapeutic effects. This guideline standardizes the diagnosis and treatment process of rotator cuff tear from the aspects of range, terminology and definition, diagnosis, TCM syndrome differentiation, treatment, functional exercise, and prevention and care. It makes recommendations that cover the adoption of manual therapy, acupuncture, and other integrative medicine based on TCM. Users of these guidelines are most likely to include clinicians and health managers in healthcare settings.


Subject(s)
Medicine, Chinese Traditional , Rotator Cuff Injuries , Humans , Rotator Cuff Injuries/therapy , Rotator Cuff Injuries/diagnosis , Integrative Medicine , Practice Guidelines as Topic , Drugs, Chinese Herbal/therapeutic use
12.
J Biomater Sci Polym Ed ; 35(6): 799-822, 2024 04.
Article in English | MEDLINE | ID: mdl-38289681

ABSTRACT

Nowadays, cartilage tissue engineering (CTE) is considered important due to lack of repair of cartilaginous lesions and the absence of appropriate methods for treatment. In this study, polycaprolactone (PCL) scaffolds were fabricated by three-dimensional (3D) printing and were then coated with fibrin (F) and acellular solubilized extracellular matrix (ECM). After extracting adipose-derived stem cells (ADSCs), 3D-printed scaffolds were characterized and compared to hydrogel groups. After inducing the chondrogenic differentiation in the presence of Piascledine and comparing it with TGF-ß3 for 28 days, the expression of genes involved in chondrogenesis (AGG, COLII) and the expression of the hypertrophic gene (COLX) were examined by real-time PCR. The expression of proteins COLII and COLX was also determined by immunohistochemistry. Glycosaminoglycan was measured by toluidine blue staining. 3D-printed scaffolds clearly improved cell proliferation, viability, water absorption and compressive strength compared to the hydrogel groups. Moreover, the use of compounds such as ECM and Piascledine in the process of ADSCs chondrogenesis induction increased cartilage-specific markers and decreased the hypertrophic marker compared to TGF-ß3. In Piascledine groups, the expression of COLL II protein, COLL II and Aggrecan genes, and the amount of glycosaminoglycan showed a significant increase in the PCL/F/ECM compared to the PCL and PCL/F groups.


Subject(s)
Mesenchymal Stem Cells , Phytosterols , Plant Extracts , Polyesters , Tissue Scaffolds , Vitamin E , Tissue Scaffolds/chemistry , Chondrogenesis , Transforming Growth Factor beta3/pharmacology , Cartilage , Tissue Engineering/methods , Extracellular Matrix/metabolism , Glycosaminoglycans , Cell Differentiation , Printing, Three-Dimensional , Hydrogels/metabolism , Drug Combinations
13.
Aging (Albany NY) ; 16(2): 1145-1160, 2024 01 26.
Article in English | MEDLINE | ID: mdl-38284902

ABSTRACT

Lumbar disc degeneration (LDD) is a prevalent clinical spinal disease characterized by the calcification and degeneration of the cartilage endplate (CEP), which significantly reduces nutrient supply to the intervertebral disc. Traditional Chinese medicine offers a conservative and effective approach for treating LDD. We aimed to investigate the molecular mechanisms underlying the therapeutic effects of Sesamin in LDD treatment. Transcriptome sequencing was used to analyze the effect of Sesamin on LPS-induced ATDC5. We explored the role of BECN2, a target gene of Sesamin, in attenuating LPS-induced degeneration of ATDC5 cells. Our results revealed the identification of 117 differentially expressed genes (DEGs), with 54 up-regulated and 63 down-regulated genes. Notably, Sesamin significantly increased the expression of BECN2 in LPS-induced ATDC5 cell degeneration. Overexpressed BECN2 enhanced cell viability and inhibited cell apoptosis in LPS-induced ATDC5 cells, while BECN2 knockdown reduced cell viability and increased apoptosis. Furthermore, BECN2 played a crucial role in attenuating chondrocyte degeneration by modulating autophagy and inflammation. Specifically, BECN2 suppressed autophagy by reducing the expression of ATG14, VPS34, and GASP1, and alleviated the inflammatory response by decreasing the expression of inflammasome proteins NLRP3, NLRC4, NLRP1, and AIM2. In vivo experiments further supported the beneficial effects of Sesamin in mitigating LDD. This study provides novel insights into the potential molecular mechanism of Sesamin in treating LDD, highlighting its ability to mediate autophagy and inflammation inhibition via targeting the BECN2. This study provides a new therapeutic strategy for the treatment of LDD, as well as a potential molecular target for LDD.


Subject(s)
Dioxoles , Intervertebral Disc Degeneration , Intracellular Signaling Peptides and Proteins , Lignans , Autophagy , Cartilage/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Intervertebral Disc Degeneration/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Lipopolysaccharides/pharmacology , Animals , Mice
14.
Article in English | MEDLINE | ID: mdl-38290792

ABSTRACT

OBJECTIVE: Cartilage pathologic calcification is a hallmark of osteoarthritis (OA). Here, we aimed to describe a new ex vivo human model to study the progression of cartilage calcification. METHOD: Cartilage explants (n = 11), as well as primary chondrocytes (n = 3), were obtained from OA patients undergoing knee replacement. Explants and chondrocytes were cultured in control (NT) or calcification (CM) medium (supplemented with ascorbic acid and ß-glycerophosphate). Calcification was evaluated by micro-CT scan at day 0 and 21 in explants, and by Alizarin red staining in chondrocyte monolayers. Raman spectrometry allowed characterization of the crystal type. Interleukin-6 (IL-6) secretion in explant and cell supernatants was measured by ELISA. Finally, matrix degradation was evaluated by Safranin-O staining of explant sections and by glycosaminoglycans (GAG) release in supernatants. RESULTS: Micro-CT scan showed calcifications in all explants at baseline (day 0), which in the CM group increased significantly in number and size after 21 days compared with the NT group. Raman spectrometry revealed that crystals were exclusively basic calcium phosphate crystals (carbonated hydroxyapatite) both in NT and CM. IL-6 secretion was significantly increased in calcifying conditions. Finally, CM significantly increased cartilage catabolism as assessed by decreased Safranin-O staining of tissue explants and increased GAG release in supernatants. CM effects (enhanced calcification, IL-6 secretion and proteoglycans turn-over) were recapitulated in vitro in OA chondrocytes. CONCLUSIONS: We have described a new ex vivo human model of cartilage calcification that can summurize the triad of events seen during osteoarthritis progression, i.e. calcification, inflammation, and cartilage degradation. This model will allow the identification of new anti-calcification compounds.

15.
J Tradit Complement Med ; 14(1): 26-39, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38223812

ABSTRACT

Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1ß induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis.

16.
Int Orthop ; 48(1): 279-290, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37646823

ABSTRACT

PURPOSE: Mesenchymal stem cells/medicinal signaling cells (MSCs) possess therapeutic potential and are used in regenerative orthopaedics. The infra-patellar fat pad (IFP) is partially resected during knee arthroscopy (KASC) and contains MSCs. Heat, irrigation, and mechanical stress during KASC may decrease MSC's therapeutic potential. This study assessed MSCs' regenerative potential after arthroscopic IFP harvest and potential effects of two blood products (BP) (platelet-rich plasma (PRP), hyperacute serum (HAS)) on MSCs' viability and chondrogenic differentiation capacity. METHODS: IFP was arthroscopically harvested, isolated, and counted (n = 5). Flow cytometry was used to assess cell viability via staining with annexin V/7-AAD and stemness markers via staining for CD90, CD73, and CD105. MSCs were incubated with blood products, and metabolic activity was determined via an XTT assay. Deposition of cartilage extracellular matrix was determined in histologic sections of chondrogenically differentiated 3D pellet cultures via staining with Alcian Blue. Expression of cartilage-specific genes (SOX9, MMP3/13, ACAN, COL1/2) was analyzed via quantitative PCR. RESULTS: MSC isolation from IFP yielded 2.66*106 ± 1.49*106 viable cells from 2.7 (0.748) g of tissue. MSC markers (CD 90/105/73) were successfully detected and annexin V staining showed 81.5% viable cells. XTT showed increased metabolic activity. Within the BP groups, this increase was significant (days 0-14, p < 0.05). PCR showed expression of cartilage-specific genes in each group. COL2 (p < 0.01) as well as ACAN (p < 0.001) expression levels were significantly higher in the HAS group. Histology showed successful differentiation. CONCLUSION: Arthroscopic harvest of IFP-MSCs yields sufficient cells with maintained regenerative potential and viability. Blood products further enhance MSCs' viability.


Subject(s)
Adipose Tissue , Mesenchymal Stem Cells , Humans , Annexin A5/metabolism , Cells, Cultured , Cell Differentiation , Dietary Supplements , Chondrogenesis
17.
Int J Biol Macromol ; 257(Pt 2): 128594, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38056744

ABSTRACT

Natural polymers and its mixtures in the form of films, sponges and hydrogels are playing a major role in tissue engineering and regenerative medicine. Hydrogels have been extensively investigated as standalone materials for drug delivery purposes as they enable effective encapsulation and sustained release of drugs. Biopolymers are widely utilised in the fabrication of hydrogels due to their safety, biocompatibility, low toxicity, and regulated breakdown by human enzymes. Among all the biopolymers, polysaccharide-based polymer is well suited to overcome the limitations of traditional wound dressing materials. Pectin is a polysaccharide which can be extracted from different plant sources and is used in various pharmaceutical and biomedical applications including cartilage regeneration. Pectin itself cannot be employed as scaffolds for tissue engineering since it decomposes quickly. This article discusses recent research and developments on pectin polysaccharide, including its types, origins, applications, and potential demands for use in AI-mediated scaffolds. It also covers the materials-design process, strategy for implementation to material selection and fabrication methods for evaluation. Finally, we discuss unmet requirements and current obstacles in the development of optimal materials for wound healing and bone-tissue regeneration, as well as emerging strategies in the field.


Subject(s)
Neoplasms , Tissue Engineering , Humans , Tissue Engineering/methods , Pectins/pharmacology , Neoplasms/drug therapy , Tissue Scaffolds , Cartilage , Polysaccharides/therapeutic use , Polysaccharides/pharmacology , Wound Healing , Biopolymers/pharmacology , Polymers/pharmacology , Hydrogels/pharmacology , Biocompatible Materials/pharmacology
18.
J Clin Med ; 12(23)2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38068394

ABSTRACT

Articular cartilage lesions negatively affect patients' well-being, causing severe pain and significantly limiting functioning. The purpose of this study was to evaluate the effectiveness of a one-stage reconstruction, performed arthroscopically using a hyaluronate-based scaffold. Pain reduction and functional improvement were assessed. The study also evaluated if postoperative vitamin D supplementation and rehabilitation protocol impact obtained outcomes. A group of 29 patients was included in a retrospective study. All the participants underwent arthroscopic reconstruction of osteochondral lesions using hyaluronate-based scaffolds. The study group used standard questionnaires to self-assess their condition before surgery and at the time of completion. Despite the aforementioned, all the participants fulfilled two original questionnaires on postoperative rehabilitation and vitamin D supplementation. Significant pain reduction (mean NRS 1.83 vs. 7.21, p < 0.0001) and functional improvement (mean Lysholm score 82.38 vs. 40.38, p < 0.0001; mean OKS 40.2 vs. 23.1, p < 0.0001) were found. No differences in pain reduction and functional improvement were seen between genders. The impact of post-operative rehabilitation and vitamin D supplementation on clinical outcomes was found to be statistically nonsignificant. The results obtained in this study clearly confirm the effectiveness of osteochondral reconstruction using hyaluronate-based scaffolds. The outcomes were equally favorable, regardless of postoperative rehabilitation and vitamin D supplementation.

19.
J Avian Med Surg ; 37(3): 235-242, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37962317

ABSTRACT

A retrospective cross-sectional study was performed to measure the prevalence of avian intertarsal inflammation over a 5-year period, identify risk factors, and discuss treatment options. The authors hypothesized that: 1) long-legged birds would be more affected, 2) participation in a bird show would be a significant risk factor, and 3) young animals would be more frequently affected. Thirty-five clinical cases from 9 avian orders were included in the study. Statistical analysis indicated that the orders Ciconiiformes (9/150; 6%, 95% confidence interval [CI]: 3.2-11), Gruiformes (4/132; 3%, 95% CI: 1.2-7.5), and Pelecaniformes (7/152; 2.8%, 95% CI: 1.4-5.6) were significantly more affected than other orders (P < 0.01). Similarly, long-legged birds (21/35) had 9.8 times greater chance (P < 0.001, 95% CI: 4.7-21) of developing the condition compared with other birds. Participation in a free-flight show (22/35) was a significant risk factor (P < 0.001; odds ratio: 7.0, 95% CI: 3.3-15). Mean age at onset of clinical signs was 5.7 years, and being < 2 years-of-age during the study period was not a significant predictor of disease (P = 0.054). The tibial cartilage, a fragile fibrocartilaginous structure, was frequently affected (34%, 12/35). Treatment protocols included anti-inflammatory drugs, analgesic drugs, or both (94%, 33/35), low-level laser therapy (54%, 19/35), joint immobilization (34%, 12/35), intra-articular corticoid injections (20%, 7/35), surgical stabilization (17%, 6/35), physiotherapy (9%, 3/35), intra-articular hyaluronic acid (6%, 2/35) or platelet-rich plasma (3%, 1/35) injections, and chiropractic care (3%, 1/35). Overall recovery rate was 49% (17/35), and the condition was associated with a poor prognosis in chronic cases.


Subject(s)
Hyaluronic Acid , Inflammation , Animals , Retrospective Studies , Cross-Sectional Studies , Inflammation/veterinary , Hyaluronic Acid/therapeutic use , Birds
20.
Foot Ankle Surg ; 29(8): 611-615, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37953101

ABSTRACT

BACKGROUND: Recently, herbal medicine has become alternative in management of gout. Our aim is to assess effectiveness of purple sweet potato extract in gout. METHOD: In vivo study with randomized posttest only control group design. Purple sweet potato extract administered to 16 Wistar rats with MSU-induced gout. Independent t-test for analyzing interleukin-1 ß (IL-1ß), matrix metalloproteinase-3 (MMP-3), cartilage oligomeric matrix protein (COMP), malondialdehyde (MDA), and number of chondrocytes results. RESULTS: Decreased level of IL-1ß (3.81 ± 1.54 ng/mL vs. 2.55 ± 0.59 ng/mL, p = 0.04), MDA (5.04 ± 1.02 ng/mL vs. 2.27 ± 0.57 ng/mL, p = 0.04), MMP-3 (5.66 ± 1.02 ng/mL vs. 3.84 ± 1.37 ng/mL, p = 0.01) COMP (21.01 ± 3.57 ng/mL vs. 17.27 ± 2.60 ng/mL, p = 0.03), and increasing chondrocytes (35.17 ± 12.35 lp vs. 48.56 ± 7.17 lp, p = 0.02). CONCLUSION: Purple sweet potato extract with anthocyanin inhibits inflammation and cartilage degeneration in gout. LEVEL OF EVIDENCE: Level 1.


Subject(s)
Gout , Ipomoea batatas , Rats , Animals , Humans , Rats, Wistar , Ipomoea batatas/metabolism , Matrix Metalloproteinase 3/metabolism , Chondrocytes , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/metabolism
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