Cartilage Disorders Research Articles

Exploring bovine three-dimensional chondrocyte culture models in osteoarthritis research: A systematic review

Background: The use of different animal species for chondrocyte culture has been employed to investigate the diseases that affect cartilage, including osteoarthritis. Bovine cartilage and chondrocytes can be used to establish three-dimensional cell cultures, which offer a more dependable in vitro model when compared to conventional monolayer cultures. However, bovine chondrocytes in three-dimensional cultures have not been widely implemented, losing a potential source of mammal tissue that could prove valuable for preclinical studies on osteoarthritis. Objective: The objective of this study was to conduct a comprehensive review of the existing scientific literature that employs three-dimensional cultures of bovine cartilage to investigate osteoarthritis. Methods: A systematic search was performed using the electronic databases PubMed and Scopus, to identify clinical studies using 3D cell culture for osteoarthritis. Search terms included: ´3D culture’, ‘3D cell culture’, ‘bovine cartilage’ and ‘chondrocyte’. A total of 59 articles were gathered, and after screening, 12 articles were included in the final analysis. Risk of bias assessment was conducted categorizing each of the studies as having a 'low,' 'medium,' or 'high' risk of bias. Results: Analysis of the articles included in this review highlighted the increased variability in harvesting sites involving carpal, metacarpal, and knee joints, as well as variation in culture methods utilizing cell passages ranging from passage zero to passage nine. Moreover, medium, and high risk of bias were detected in all the articles probably due to challenges in randomization and blinding of the studies. In summary, this review critically examines three-dimensional cell culture for the investigation of cartilage disorders, with a particular emphasis on bovine cartilage. Conclusions: Future studies should include consistent methods across the in vitro phase of the study, such as uniform harvest sites, as well as using early chondrocyte passages to preserve cellular phenotype. Furthermore, comparison of relevant translational models should include age-matched conditions to avoid further confounding factors.

Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices

Currently, analgesics, anti-inflammatory drugs, and hyaluronic acid viscosupplementation are used to alleviate pain associated with joint cartilage disorders. Hyaluronic acid injections are known not only for their pain-reducing effects but also for stimulating cartilage regeneration. In this study, a regenerative biomaterial platform comprising poly (glycolic acid) mesh and cross-linked hyaluronic acid was developed for the repair of degenerated joint cartilage following microfracture and subchondral bone stimulation. For this purpose, in the first stage, hyaluronic acid gels cross-linked with butanediol diglycidyl ether, containing a concentration of 23 mg/mL, were prepared. The residual butanediol diglycidyl ether cross-linker in the obtained gels was below 1 ppb. The pH value was determined to be 6.95 ± 0.2, and the osmolality was 361.3 ± 2.9 mOsm/kg. The injection force and related rheological properties were investigated. In the second stage, the cross-linked hyaluronic acid gels were impregnated into poly (glycolic acid) meshes, evaluated using scanning electron microscopy and characterized chemically. Finally, the composite matrices were recellularized with chondrocytes, and cell viability analysis was conducted using Alamar Blue. The Alamar Blue results and scanning electron microscopy images of the composite structure consisting of poly (glycolic acid) mesh and cross-linked hyaluronic acid indicated that the structure supports chondrocyte viability.

Trends of ankle arthroscopy in Italy: Analysis of an official national database

ObjectivesAnkle arthroscopy has become increasingly popular as a less invasive surgical diagnostic and therapeutic procedure for a variety ankle disorder previously managed with open surgery. Despite literature reports encouraging outcomes and low complication rates, nationwide trends in ankle arthroscopy have been poorly investigated. To fully understand the burden of an emerging surgical approach as well as helping to create global standards for the diagnosis and treatment of ankle diseases, this study aimed to evaluate the incidence and demographics of patients undergoing ankle arthroscopy in Italy from 2001 to 2016. MethodsData were obtained from the National Hospital Discharge Records (SDO) provided by the Italian Ministry of Health. The patient's age, gender, length of hospital stays, primary diagnosis, and primary procedure are among the anonymized data. Population data were obtained from the National Institute for Statistics (ISTAT). According to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) ankle arthroscopy was defined by the following procedure code: 80.27. ResultsA total of 23,644 procedures were performed in Italy. The 25 to 29 and 30 to 34 age groups underwent this type of surgery at most. The majority of patients were males. The median length of hospital stay was 2.1 ​± ​2.3 days. Each year in Italy, this surgery costs an average of 2,133,401€ ± 342,143€. The main primary codified diagnoses were: “contracture of joint, ankle and foot” (13.4 ​%), “articular cartilage disorder, ankle and foot” (8.6 ​%), “late effect of sprain and strain without mention of tendon injury” (7.5 ​%) and “other joint derangement, not elsewhere classified, ankle and foot” (6.4 ​%). ConclusionsThe present study evaluated the burden of ankle arthroscopy on the national health care system and the distribution of the main diseases requiring this type of surgery. Surgeons and policy makers can allocate healthcare resources more effectively and provide patients with high-quality care by having a better understanding of national practice patterns. Level of EvidenceIII.

Prenatal Ultrasonographic Features Associated With ARSL and X-Linked Chondrodysplasia Punctata 1 (CDPX1): Literature Review and Case Series.

Chondrodysplasia punctata 1 (CDPX1) is an X-linked recessive disorder of cartilage and bone development characterized by stippling on the cartilage and bone, flattened nasal bridge, and brachydactyly, or short fingers. CDPX1 has been associated with variants in the ARSL gene and is known to manifest prenatally, however, there has been no systematic literature review on this evidence. Here, we reviewed the current literature on prenatal manifestations of CDPX1, and additionally introduce previously unpublished cases. A systematic review of the literature was performed. Additionally, a GeneMatcher submission was created and a call for cases was presented at the Fetal Sequencing Consortium meetings to find previously unpublished cases. For the 22 fetuses reported here, we found that 55% had nasal hypoplasia, 41% had bony stippling or calcifications, 32% had polyhydramnios, 5% had oligohydramnios, 23% had shortened long bones, 23% had spinal canal stenosis, 18% had ventriculomegaly, 9% had brachydactyly/brachytelephalangy, 9% had clubbed feet, 9% had premature rupture of membranes, and 9% had intraventricular hemorrhage detected through sonography or radiography. We also found 17 unique variants in ARSL for these 22 fetuses. A previously unpublished association of ARSL variants with intrauterine fetal death or stillbirth has been noted in this study. It is also possible that intracranial hemorrhage is an underrecognized feature associated with CDPX1 variation. However, there have been challenges in applying ACMG criteria to ARSL, a gene without an associated Variant Curation Expert Panel. This literature review and case series highlights which features of CDPX1 manifest prenatally, as well as introduces new phenotypes that have not been previously identified.

MSCs derived membrane coating nanoparticles targeted delivery itaconic acid to regulate M1 macrophage pyroptosis for osteoarthritis therapy

Osteoarthritis (OA) is a common chronic inflammatory disorder and a major cause of disability. Previous studies have shown that M1 macrophages play an important role in promoting increased inflammation in OA. And because the activated M1 macrophages highly expresses folate receptors, folate (FA) modified nanoparticles provide a new method for targeted drug delivery to macrophages. In this study, we reported itaconic acid (ITA) loaded nanoparticles encapsulated in FA modified cell membranes (FMINPs) as a potential therapeutic agent for OA treatment. This negative charged system has a core-shell structure with a particle size of 162.3 ± 3.65 nm and the system could slowly release ITA within 7 days. The cellular uptake of nanoparticles increased after FA modification. Importantly, the nanoparticles could inhibit the pyroptosis behavior of M1 macrophages by reducing the activity of NLRP3/capase-1/GSDMD protein, thereby alleviating the inhibitory effect of inflammatory microenvironment on mesenchymal stem cells (MSCs) activity and chondrogenic differentiation. Intra-articular injection of nanoparticles protected joint cartilage against OA development and reduced inflammatory response in the OA rat model. All in all, as a potential therapeutic agent, this system can target FA receptor for OA treatment, and the NLRP3/capase-1/GSDMD axis is indicated as an underlying mechanism of destructive cartilage disorders.

An Isotonic Drink Containing Pacific Cod (Gadus macrocephalus) Processing Waste Collagen Hydrolysate for Bone and Cartilage Health.

Malnutrition is one of the major factors of bone and cartilage disorders. Pacific cod (Gadus macrocephalus) processing waste is a cheap and highly promising source of bioactive substances, including collagen-derived peptides and amino acids, for bone and cartilage structure stabilization. The addition of these substances to a functional drink is one of the ways to achieve their fast intestinal absorption. Collagen hydrolysate was obtained via enzymatic hydrolysis, ultrafiltration, freeze-drying, and grinding to powder. The lyophilized hydrolysate was a light gray powder with high protein content (>90%), including collagen (about 85% of total protein) and a complete set of essential and non-essential amino acids. The hydrolysate had no observed adverse effect on human mesenchymal stem cell morphology, viability, or proliferation. The hydrolysate was applicable as a protein food supply or a structure-forming food component due to the presence of collagen fiber fragments. An isotonic fitness drink (osmolality 298.1 ± 2.1 mOsm/L) containing hydrolysate and vitamin C as a cofactor in collagen biosynthesis was prepared. The addition of the hydrolysate did not adversely affect its organoleptic parameters. The production of such functional foods and drinks is one of the beneficial ways of fish processing waste utilization.

Monosodium iodoacetate induces Cartilage degradation and inflammation in rats in a dose- and time-dependent manner

Monosodium iodoacetate (MIA) is a widely recognized agent for inducing cartilage degradation and inflammation in animal models. In this study, we systematically investigated the dose- and time-dependent effects of MIA on cartilage degradation in the knees of rats. We evaluated knee diameter, knee bend score, and the levels of pro-inflammatory cytokines (IL-1 and IL-8) and cartilage degradation markers (CTX-II) to gain insights into cartilage damage and inflammation progression. Wistar rats were categorized into groups receiving various doses of MIA via intra-articular injection (0.1 mg, 0.5 mg, 1 mg, 3 mg, and 5 mg) and were observed at multiple time intervals (2, 4, 6, 8, 10, and 12 weeks). We measured knee diameter to gauge joint swelling, assigned knee bend scores to assess functional limitations, and analyzed synovial fluid samples for IL-1β, IL-8, and CTX-II levels. Our data show that low-dose MIA increases pain sensitivity, knee diameter, inflammatory cytokines IL-1β and IL-8, and CTX-II levels, which progress slowly over 12 weeks. On the other hand, higher dosages of MIA caused cartilage deterioration after two weeks, followed by an increase in inflammatory cytokines. This research sheds light on MIA administration's dose- and time-dependent effects on cartilage breakdown and inflammation in rat knee joints. Analyzing knee diameter, knee bend score, IL-1β, IL-8, and CTX-II as evaluation parameters provides a multidimensional perspective of cartilage injury and inflammatory dynamics. These findings help us comprehend cartilage-related illnesses and have implications for future research on therapeutic approaches for cartilage disorders.

Hypoxic Conditions Modulate Chondrogenesis through the Circadian Clock: The Role of Hypoxia-Inducible Factor-1α.

Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor composed of an alpha and a beta subunit. HIF-1α is a master regulator of cellular response to hypoxia by activating the transcription of genes that facilitate metabolic adaptation to hypoxia. Since chondrocytes in mature articular cartilage reside in a hypoxic environment, HIF-1α plays an important role in chondrogenesis and in the physiological lifecycle of articular cartilage. Accumulating evidence suggests interactions between the HIF pathways and the circadian clock. The circadian clock is an emerging regulator in both developing and mature chondrocytes. However, how circadian rhythm is established during the early steps of cartilage formation and through what signaling pathways it promotes the healthy chondrocyte phenotype is still not entirely known. This narrative review aims to deliver a concise analysis of the existing understanding of the dynamic interplay between HIF-1α and the molecular clock in chondrocytes, in states of both health and disease, while also incorporating creative interpretations. We explore diverse hypotheses regarding the intricate interactions among these pathways and propose relevant therapeutic strategies for cartilage disorders such as osteoarthritis.

Knee injury and osteoarthritis outcome score (KOOS): Validity and reliability of an Indonesian version

Background: One of the health problems that often occurs in old age is musculoskeletal disorder, especially osteoarthritis which is a disorder of the joint cartilage. Knee injury and osteoarthritis outcome score is one of the measuring tools uses to access the function of patient with knee injuries and knee osteoarthritis. Purpose: To determine the cross-cultural adaption of modifications to the Indonesia version of the knee injury and osteoarthritis outcome score questionnaire by conducting validity and reliability tests. Method: This research was conducted in September 2023 at Islamic General Hospital Kustati and Sebelas Maret University Hospital with a sample size of 55 participants. Sampling was carried out using purposive sampling technique. The KOOS instrument was given 2 times with an interval of 2 weeks. Results: The test-retest reliability result of the Indonesia version of the KOOS instrument between the two measurement sessions were very good (ICC 0.965, p<0.001, and 95% CI: 0.939-0.979). Internal consistency was confirmed to be very good with the Cronbach’s alpha test of 0.974. Conclusion: Based on the content validity result shown, there are 39 items with corrected correlation item values above 0.3 the conclusion was the Indonesia version of the KOOS instrument declaring reliable, but the content validity of the 2 items needs to be re-examined.

Kesehatan Sendi Optimal : Edukasi Osteoarthritis Bagi Lansia di Desa Gedongan

Osteoarthritis is a cartilage disorder in the joints of bones that often affects elderly people. As many as 24 million people in the Southeast Asia region and 151 million people worldwide suffer from osteoarthritis. The community service practice aims to provide education to elderly people with osteoarthritis. The sampling technique was purposive sampling with 85 elderly respondents. The level of knowledge of the elderly about osteoarthritis disease is obtained through pretest and posttest. Providing education to the elderly about osteoarthritis disease by counseling and exposure to material using posters and leaflets and demonstrations related to the handling of osteoarthritis. Analysis of research data using chi square and fisher exact tests. The results obtained in the age factor (p = 0.021), gender (p = 0.015), BMI (p = 0.002) and physical activity (p = 0.584). There is a relationship between age, gender and body mass index with the incidence of osteoarthritis in the elderly and there is no relationship between physical activity and the incidence of osteoarthritis in the elderly.

Chemokines in Cartilage Regeneration and Degradation: New Insights.

Cartilage plays a crucial role in the human body by forming long bones during development and growth to bear loads on joints and intervertebral discs. However, the increasing prevalence of cartilage degenerative disorders is a growing public health concern, especially due to the poor innate regenerative capacity of cartilage. Chondrocytes are a source of several inflammatory mediators that play vital roles in the pathogenesis of cartilage disorders. Among these mediators, chemokines have been explored as potential contributors to cartilage degeneration and regeneration. Our review focuses on the progress made during the last ten years in identifying the regulators and roles of chemokines and their receptors in different mechanisms related to chondrocytes and cartilage. Recent findings have demonstrated that chemokines influence cartilage both positively and negatively. Their induction and involvement in either process depends on the local molecular environment and is both site- and time-dependent. One of the challenges in defining the role of chemokines in cartilage pathology or regeneration is the apparent redundancy in the interaction of chemokines with their receptors. Hence, it is crucial to determine, for each situation, whether targeting specific chemokines or their receptors will help in developing effective therapeutic strategies for cartilage repair.

An Overview of the Association Between Smoking and Cartilage Disorders

An Overview of the Association Between Smoking and Cartilage Disorders

THE EFFECT OF CHRONOLOGICAL AGE AND GENDER AND DIFFERENT SOURCE OF TISSUE ON THE IN VITRO PROPERTIES OF MESENCHYMAL STROMAL CELLS

AbstractObjectivesOsteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age and gender is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age and gender on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties.Methods and ResultsWe initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age and gender on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory-based experiments to assess these properties. Compare the extent of the effect of age on MSC cell marker expression, proliferation and pathways. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the synovium, fat pad and bone fragments using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for antibody cocktail (eg included CD34, CD45). The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. At P2 after extracting RNA, we investigate the gene analysis using Bulk seq. Clear differences between the younger and older patients and gender were indicated.ConclusionsChronological age and gender-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age and gender on cellular senescence and identify pathways that could be targeted to potentially reverse any age and gender-related changes.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Genetic testing and diagnostic strategies of fetal skeletal dysplasia: a preliminary study in Wuhan, China

BackgroundFetal skeletal dysplasia is a diverse group of degenerative diseases of bone and cartilage disorders that can lead to movement disorder and even death. This study aims to evaluate the diagnostic yield of sonographic examination and genetic testing for fetal skeletal dysplasia.MethodsFrom September 2015 to April 2021, the study investigated 24 cases with suspected short-limb fetuses, which were obtained from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology. To identify the causative gene, multiple approaches (including karyotype analysis, copy number variations and whole exome sequencing) were performed on these fetuses. And further segregation analysis of the candidate variant was performed in parents by using Sanger sequencing.Results① Out of 24 cases, likely pathogenic variants in FGFR3, FBN2, COL1A2, CUL7 and DYNC2H1 were detected in 6 cases; pathogenic variants in FGFR3, IMPAD1 and GORAB were identified in other 6 cases; and variants in WNT1, FBN1, OBSL1, COL1A1, DYNC2H1 and NEK1, known as Variant of Undetermined Significance, were found in 4 cases. There were no variants detected in the rest 8 cases by the whole exome sequencing. ② Of 24 cases, 12 (50%) were found to carry variants (pathogenic or likely pathogenic) in seven genes with 12 variants. Four fetuses (16.7%) had variants of uncertain significance.ConclusionGenetic testing combining with ultrasound scanning enhances the accurate diagnosis of fatal skeletal dysplasia in utero, and then provides appropriate genetic counseling.

Five siblings expand the spectrum of GPC6-related skeletal dysplasia.

Skeletal dysplasias broadly include disorders of cartilage or bone. Omodysplasia-1 is a type of skeletal dysplasia caused by biallelic loss of function variants in the GPC6 gene. GPC6 codes for the protein glypican 6 (GPC6) (OMIM *604404), which stimulates bone growth. We report a family in which five out of nine children were presented with a skeletal dysplasia characterized phenotypically by mild short stature and rhizomelia. All affected individuals were found to have homozygous missense variants in GPC6: c.511 C>T (p.Arg171Trp). Radiograph findings included rhizomelic foreshortening of all four extremities, coxa breva, and ulna minus deformity. Using a Hedgehog (Hh) reporter assay, we demonstrate that the variant found in this family results in significantly reduced stimulation of Hh activity when compared to the wild-type GPC6 protein, however protein function is still present. Thus, the milder phenotype seen in the family presented is hypothesized due to decreased GPC6 protein activity versus complete loss of function as seen in omodysplasia-1. Given the unique phenotype and molecular mechanism, we propose that this family's findings widen the phenotypic spectrum of GPC6-related skeletal dysplasias.

Blockage of Osteopontin-Integrin β3 Signaling in Infrapatellar Fat Pad Attenuates Osteoarthritis in Mice.

The knowledge of osteoarthritis (OA) has nowadays been extended from a focalized cartilage disorder to a multifactorial disease. Although recent investigations have reported that infrapatellar fat pad (IPFP) can trigger inflammation in the knee joint, the mechanisms behind the role of IPFP on knee OA progression remain to be defined. Here, dysregulated osteopontin (OPN) and integrin β3 signaling are found in the OA specimens of both human and mice. It is further demonstrated that IPFP-derived OPN participates in OA progression, including activated matrix metallopeptidase 9 in chondrocyte hypertrophy and integrin β3 in IPFP fibrosis. Motivated by these findings, an injectable nanogel is fabricated to provide sustained release of siRNA Cd61 (RGD- Nanogel/siRNA Cd61) that targets integrins. The RGD- Nanogel possesses excellent biocompatibility and desired targeting abilities both in vitro and in vivo. Local injection of RGD- Nanogel/siRNA Cd61 robustly alleviates the cartilage degeneration, suppresses the advancement of tidemark, and reduces the subchondral trabecular bone mass in OA mice. Taken together, this study provides an avenue for developing RGD- Nanogel/siRNA Cd61 therapy to mitigate OA progression via blocking OPN-integrin β3 signaling in IPFP.

The Development of Naringin for Use against Bone and Cartilage Disorders.

Bone and cartilage disorders are the leading causes of musculoskeletal disability. There is no absolute cure for all bone and cartilage disorders. The exploration of natural compounds for the potential therapeutic use against bone and cartilage disorders is proving promising. Among these natural chemicals, naringin, a flavanone glycoside, is a potential candidate due to its multifaceted pharmacological activities in bone and cartilage tissues. Emerging studies indicate that naringin may promote osteogenic differentiation, inhibit osteoclast formation, and exhibit protective effects against osteoporosis in vivo and in vitro. Many signaling pathways, such as BMP-2, Wnt/β-catenin, and VEGF/VEGFR, participate in the biological actions of naringin in mediating the pathological development of osteoporosis. In addition, the anti-inflammatory, anti-oxidative stress, and anti-apoptosis abilities of naringin also demonstrate its beneficial effects against bone and cartilage disorders, including intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, bone and cartilage tumors, and tibial dyschondroplasia. Naringin exhibits protective effects against bone and cartilage disorders. However, more efforts are still needed due to, at least in part, the uncertainty of drug targets. Further biological and pharmacological evaluations of naringin and its applications in bone tissue engineering, particularly its therapeutic effects against osteoporosis, might result in developing potential drug candidates.

THE EFFECT OF CHRONOLOGICAL AGE ON THE IN VITRO PROPERTIES OF BONE FRAGMENT-DERIVED MESENCHYMAL STROMAL CELLS

Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties.We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory based experiments to assess these properties. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the bone fragments using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for CD34 and CD45. The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. Clear differences between the younger and older patients were indicated.Chronological age-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age on cellular senescence and identify pathways that could be targeted to potentially reverse any age-related changes.

Application of stem cell therapy for osteoarthritis pain management.

Osteoarthritis (OA) is a degenerative bone disease that results in inflammation of the joint cartilage. Approximately 58 million adults in the world are affected by this disease, which is characterized by pain, stiffness, and decrease in bone density. The current medication for the treatment of OA is non-steroidal anti-inflammatory drugs (NSAID), opioids, and cyclooxygenase (COX)-2-specific drugs which reduce the pain but do not improve the cartilage disorder. The marketed available drugs for the treatment of OA have gastrointestinal, cardiovascular, and addiction problems. To overcome the limitations of knee OA drug treatment, stem-cell-based therapy is being utilized to recover the knee from the pain and regenerate the cartilage from its recent damaged state. The objective of this study is to effectively manage osteoarthritis by Human Mesenchymal Stem Cell (hMSC) delivery to bone cartilage. In our study, OA in rat knees was produced by intra-articular papain enzyme injections and was observed by pain behavior assay. Latencies in rats treated by papain enzyme were significantly decreased compared to saline. We observed that female rats produced more arthritis by papain enzyme than male rats. The results of the hot plate test showed that the paw-withdrawal threshold was significantly decreased by stem cell administration. We found 52% response by von Frey test in enzyme treated with stem cell delivery osteoarthritis rats, whereas above 80% response was observed in only enzyme treated rats. In this study, we observed that stem cell delivery contributes to the suppression of cartilage degradation in rat knees. Our research demonstrates that stem cell therapy could be a promising treatment in terms of combating tissue regeneration of rat knees to improve the pain state in the target area.

The Role of Mitochondria in Cartilage Degenerative Disorders

Mitochondria are major organelles that produce energy for cellular metabolism and are vital to proper cell functioning. Metabolic dysregulation is a critical contributing factor to the initiation and development of degenerative and autoimmune diseases, thus is present in cartilage disorders such as osteoarthritis and rheumatoid arthritis. Mitochondrial dysfunction in cartilage diseases is especially interesting because it may present a promising therapeutic and anti-ageing target. By understanding the mechanism of mitochondrial dysfunction, we can aim to upregulate the role of mitochondria in treating cartilage diseases. In this review, we look at the role of mitochondrial dysfunction in degenerative cartilage diseases and mitochondria as tools in the treatment of osteoarthritis and rheumatoid arthritis.