Cartilage Synthesis Research Articles

Increased Cartilage Synthesis Is Associated With Cumulative Bone Stimulus And Season Long Injury Incidence

Increased Cartilage Synthesis Is Associated With Cumulative Bone Stimulus And Season Long Injury Incidence

Immunomodulatory Effect of Vitamin D3 in Rats with Induced Osteoarthritis

Background: The (OA) caused by imbalance between anabolic and catabolic processes within the cartilage ,one of the effects of increased catabolic changes is presence of products of extracellular matrix degradation in the synovial fluid which lead to the joint microenvironment alteration which attempt. Aim of study: Evaluate the influence of induce osteoarthritis (OA) on knee joint and looking on (OA) effect as local immune response in addition to the possible role of vitamin (D3) as protective and repairing agent against (OA) complications. Methods: Total number of rats male (89) were used and divided into three groups, first group (control group) (19) rats, second group (OA induced) (35) rats injected with papain enzyme at dose of (10 mg), treated group (35) rats which firstly injected with papain enzyme at dose (10 mg) then after (2) weeks of injection, treated the rats with vitamin D. Results and Dicussion: Macroscopic observations revealed to cartilage surface erosion , fibrillation , hypertrophied condyles, degeneration. The rats knee joints that treated (2) weeks with vitamin (D3) post (OA) induced showed smooth, intact cartilage surface. Radiographic images indicated to narrowing joints cavity (space) at knee joint of (OA) rat model, destruction of epiphyseal plate, while the results related to (OA) rats treated with vitamin (D3) showed no osteophyte growth , the synovial cavity nearest to the normal, no defect. Conclusion: Vitamin (D) prevent the stability and life of chondrocytes which lead to cartilage protection and synthesis of (ECM) , and inhibite the inflammation resulted from cartilage damaged.

Effect of moxibustion on plasma amino acid metabolism in rats with knee osteoarthritis.

To observe the effect of moxibustion at "Zusanli "(ST36) on the plasma amino acid metabolism in rats with knee osteoarthritis (KOA), and to explore the amino acid metabolism mechanism of moxibustion in repairing cartilage injury in KOA. A total of 30 SD rats were randomly divided into normal, model and moxibustion groups, with 10 rats in each group. Rats in the model and moxibustion groups were injected with the mixture of L-cysteine and papain into bilateral knee joint cavity to make the KOA model. The moxibustion group received moxibustion at bilateral ST36 for 30 min, once daily for 30 days. At the end of the experiment, the swelling degree of knee joint was calculated, the mechanical pain threshold was measured by the Von Frey filament, the cartilage tissue injury was observed by HE staining, the matrix metalloproteinase-13 (MMP-13) content in the synovial tissue was detected by enzyme-linked immunosorbent assay (ELISA), and the differential amino acid metabolites in plasma were detected and screened by liquid chromatography-mass spectrometry (LC-MS). Compared with the normal group, the model group showed irregular cartilage surface, decreased number of chondrocytes, uneven distribution, and local clusters of chondrocytes；the contour of the tide line was blurred. The degree of joint swelling in the model group was higher than that in the normal group (P<0.01), the mechanical pain threshold was lower (P<0.01), and the content of MMP-13 in synovial tissue was higher (P<0.01). The contents of proline and tryptophan in the model group were down-regulated (P<0.01, P<0.05). Compared with the model group, the cartilage tissue damage and knee joint swelling were decreased(P<0.05), mechanical pain threshold was increased(P<0.05), MMP-13 content in synovial tissue and levels of glutamate and histidine expression were decreased (P<0.01, P<0.05). Moxibustion at ST36 significantly alleviated arthritis-related swelling and pain in KOA model rats, attenuated cartilage damage, and regulated levels of certain plasma amino acid metabolites. Moxibustion may regulate KOA cartilage synthesis and degradation through amino acid metabolic pathways such as proline, tryptophan, glutamate and histidine, exerting anti-inflammatory, analgesic, and protection of cartilage injury effects.

Cumulative Impact Loading and Cartilage Synthesis Biomarkers May Be Associated With Injury Risk in Female Collegiate Basketball Players

Cumulative Impact Loading and Cartilage Synthesis Biomarkers May Be Associated With Injury Risk in Female Collegiate Basketball Players

The Effect of the Overexpression or Addition of IGF1 and FGF2 in Human Chondrocytes Included in a Fibrin Matrix and Cultivated in a Dynamic Environment.

Hyaline cartilage is a highly specialized tissue. When injured, its repair capacity is low, which results in the massive destruction of the articular surface. Using tissue engineering and genetic engineering techniques, it is possible to provide a suitable microenvironment providing chondrocyte growth factors involved in the development of hyaline cartilage proteins, as well as cell proliferation and differentiation. Our aim was to stimulate the synthesis of an extracellular matrix via the chondrocytes included in a fibrin matrix through the addition or overexpression of IGF1 and/or FGF2, while maintaining a constant agitation of the culture medium. Collagen type II and glycosaminoglycans increased during the entire incubation time. In contrast, collagen type I decreased its expression under the same culture conditions, transfecting or supplementing growth factors to chondrocytes. However, chondrocytes that were not transfected or supplemented showed a general increase in the proteins analyzed in this study. The presence of IGF1 and FGF2 increased the protein synthesis of the hyaline cartilage, regardless of which one was the source of growth factors. Continuous agitation using the spinner flask allows for the adequate nutrition of chondrocytes included in the fibrin matrix. However, they require growth factors to up-regulate or down-regulate collagenous proteins.

Baicalin Maintains Articular Cartilage Homeostasis and Alleviates Osteoarthritis by Activating FOXO1.

Baicalin has been acknowledged for its anti-inflammatory properties. However, its potential impact on osteoarthritis (OA) has not yet been explored. Therefore, our study aimed to examine the effects of Baicalin on OA, both in laboratory and animal models. To evaluate its efficacy, human chondrocytes affected by OA were treated with interleukin-1β and/or Baicalin. The effects were then assessed through viability tests using the cell counting kit-8 (CCK-8) method and flow cytometry. In addition, we analyzed the expressions of various factors such as FOXO1, autophagy, apoptosis, and cartilage synthesis and breakdown to corroborate the effects of Baicalin. We also assessed the severity of OA through analysis of tissue samples. Our findings demonstrate that Baicalin effectively suppresses inflammatory cytokines and MMP-13 levels caused by collagenase-induced osteoarthritis, while simultaneously preserving the levels of Aggrecan and Col2. Furthermore, Baicalin has been shown to enhance autophagy. Through the use of FOXO1 inhibitors, lentivirus-mediated knockdown, and chromatin immunoprecipitation, we verified that Baicalin exerts its protective effects by activating FOXO1, which binds to the Beclin-1 promoter, thereby promoting autophagy. In conclusion, our results show that Baicalin has potential as a therapeutic agent for treating OA (Clinical Trial Registration number: 2023-61).

Tension regulates the cartilage phenotypic expression of endplate chondrocytes through the α-catenin/actin skeleton/Hippo pathway.

The study aimed to investigate the regulatory mechanism of intracellular tension signaling in endplate chondrocytes and its impact on extracellular matrix synthesis. Human endplate chondrocytes were subjected to tension load using Flexcell FX-5000™, and changes in phenotype, morphology, and the expression of Hippo signaling pathway and α-Catenin were assessed through various techniques. Through the overexpression of YAP and inhibition of α-Catenin, the study clarified the intracellular tension signaling pathway and its regulation of extracellular matrix synthesis in endplate cartilage. In vitro-cultured human endplate chondrocytes significantly suppressed phenotype-related genes and proteins, accompanied by distinct changes in cytoskeleton morphology. Tension activation resulted in the substantial activation of the Hippo pathway, increased phosphorylation of YAP, and reduced nuclear translocation of YAP. YAP overexpression alleviated the inhibitory effect of tension on extracellular matrix synthesis in endplate chondrocytes. Tension also upregulated the expression of α-Catenin in endplate chondrocytes, which was attenuated by inhibiting α-Catenin expression, thereby reducing the impact of tension on cytoskeletal morphology and YAP nuclear translocation. Taken together, the α-Catenin/actin skeleton/Hippo-coupled network is a crucial signaling pathway for tension signaling in endplate chondrocytes, providing potential therapeutic targets for the treatment of endplate cartilage degeneration.

Calycosin ameliorates osteoarthritis by regulating the imbalance between chondrocyte synthesis and catabolism.

Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ADTC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Comparison of growth factors isolated from exosomes present in maternal blood of cleft and non-cleft infants for identification and quantification of growth factors involved in the growth and development of cartilage.

Background Cleft lip and palate (C.L.P.) is a common congenital condition which affects the orofacial region. The aetiology of C.L.P. is multifaceted and involves genetic and environmental factors that impact the shape and position of the nasal cartilage, resulting in an asymmetrical appearance of the nose. Growth factors are crucial in regulating cartilage synthesis and repair. Exosomes have emerged as a promising cell-free drug delivery system that facilitates intercellular communication and maintains tissue homeostasis. This study identifies and quantifies the growth factors present in exosomes derived from lactating maternal blood of cleft and non-cleft infants and compares them to evaluate the differences. The study aims to assess the potential of these exosomes as a therapeutic approach for C.L.P. management. Methods Blood samples were collected from lactating mothers at Sharad Pawar Dental College and isolating plasma using centrifugation. Exosome and total protein isolation will be conducted in the laboratory, and immunoblotting will evaluate growth factors. Quantitative and comparative protein and growth factor analysis will be conducted separately for maternal blood samples. Results The growth factors responsible for cartilage growth and development will be present in maternal exosomes, potentially leading to novel therapies for C.L.P. management. The study aims to demonstrate the therapeutic potential of exosomes, as carriers of intra-cellular factors, in transporting growth factors to the required site for managing C.L.P. Conclusions Overall, by understanding the roles played by growth factors, intercellular communication, and genetic and environmental factors in the aetiology of C.L.P., this research can contribute to creating effective treatment strategies for C.L.P. management. Finding growth factors in exosomes made from the blood of nursing mothers could be a cutting-edge therapeutic strategy for treating C.L.P.

The CREB1 inhibitor 666-15 maintains cartilage homeostasis and mitigates osteoarthritis progression.

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). CREB1 was hyperactive in osteoarthritic articular cartilage, interleukin (IL)-1β-treated cartilage explants, and IL-1β- or carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-treated chondrocytes. 666-15 enhanced cell viability of OA-like chondrocytes and alleviated IL-1β- or CCCP-induced chondrocyte injury through inhibition of mitochondrial dysfunction-associated apoptosis. Moreover, inhibition of CREB1 by 666-15 suppressed expression of ADAMTS4. Additionally, 666-15 alleviated joint degeneration in an ACLT mouse model. Hyperactive CREB1 played a critical role in OA development, and 666-15 exerted anti-IL-1β or anti-CCCP effects in vitro as well as joint-protective effects in vivo. 666-15 may therefore be used as a promising anti-OA drug.

Glucosamine attenuates alcohol-induced acute liver injury via inhibiting oxidative stress and inflammation

Alcohol liver disease (ALD) is a liver disease caused by long-term heavy drinking. Glucosamine (GLC) is an amino monosaccharide that plays a very important role in the synthesis of human and animal cartilage. GLC is commonly used in the treatment of mild to moderate osteoarthritis and has good anti-inflammatory and antioxidant properties. In this study, alcoholic injury models were constructed in mice and human normal hepatocyte L02 cells to explore the protective effect and mechanism of GLC on ALD. Mice were given GLC by gavage for 30 days. Liver injury models of both mice and L02 cells were produced by ethanol. Detecting the levels of liver injury biomarkers, lipid metabolism, oxidative stress biomarkers, and inflammatory factors through different reagent kits. Exploring oxidative and inflammatory pathways in mouse liver tissue through Western blot and RT-PCR. The results showed that GLC can significantly inhibit the abnormal increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), very low density lipoprotein (VLDL), low-density lipoprotein cholesterol (LDL-C), and can significantly improve the level of high-density lipoprotein cholesterol (HDL-C). In addition, GLC intervention significantly improved alcohol induced hepatic oxidative stress by reducing the levels of malondialdehyde (MDA) and, increasing the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in the liver. Further mechanisms suggest that GLC can inhibit the expression of ethanol metabolism enzyme cytochrome P4502E1 (CYP2E1), activate the antioxidant pathway Keap1/Nrf2/HO-1, down-regulate the phosphorylation of MAPK and NF-κB signaling pathways, and thus reduce the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Therefore, GLC may be a significant candidate functional food for attenuating alcohol induced acute liver injury.

Fructose-bisphosphatase1 (FBP1) alleviates experimental osteoarthritis by regulating Protein crumbs homolog 3 (CRB3)

PurposeTo identify the role of gluconeogenesis in chondrocytes in osteoarthritis (OA).Materials and methodsCartilage samples were collected from OA patients and C57 mice and were stained with Safranin O-Fast Green to determine the severity of OA. Periodic acid Schiff staining was used to characterize the contents of polysaccharides and SA-βGal staining was used to characterize the aging of chondrocytes. Immunohistochemistry and western blotting were used to detect fructose-bisphosphatase1 (FBP1), SOX9, MMP13, P21, and P16 in cartilage or chondrocyte. The mRNA levels of fbp1, mmp13, sox9, colX, and acan were analyzed by qPCR to evaluate the role of FBP1 in chondrocytes.ResultsThe level of polysaccharides in cartilage was reduced in OA and the expression of FBP1 was also reduced. We treated the chondrocytes with IL-1β to cause OA in vitro, and then made chondrocytes overexpress FBP1 with plasma. It shows that FBP1 alleviated the degeneration and senescence of chondrocytes in vitro and that it also showed the same effects in vivo experiments. To further understand the mechanism of FBP1, we screened the downstream protein of FBP1 and found that CRB3 was significantly downregulated. And we confirmed that CRB3 suppressed the degeneration and delayed senescence of chondrocytes.ConclusionsFBP1 promoted the polysaccharide synthesis in cartilage and alleviated the degeneration of cartilage by regulating CRB3, so FBP1 is a potential target in treating OA.

Enhanced cartilage regeneration by icariin and mesenchymal stem cell-derived extracellular vesicles combined in alginate-hyaluronic acid hydrogel

ObjectiveOsteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs. Materials and methodsMSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo. ResultsEVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers. ConclusionThe MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.

254 Mineral Source Matters for Cartilage Development to Support Structural Integrity

Abstract Lameness is a welfare issue generally associated with increased growth rate. Objectives of this study were to 1) compare efficacy of inorganic (ITM) and organic trace mineral (OTM) sources on lameness incidence and effects on bone and cartilage biomarkers, and 2) determine if the biologically relevant biomarkers were detectable in saliva. Dietary treatments were fed for 70 d and included: 1) ITM sulfates, Zn-Cu-Mn supplemented at 120-20-40 mg/kg diet, and three OTMs supplemented at 80-10-20 Zn-Cu-Mn mg/kg diet, respectfully. The OTM treatments included a non-specific amino acid complex (Trt 2 – OTM complex), a glycinate (Trt 3 - OTM glycinate), and a metal methionine hydroxy analogue chelate (Trt 4 – OTM MMHAC) supplied as MINTREX trace minerals (Novus International, Inc., St Charles, MO). The study consisted of 144 barrows (56 kg initial BW; 36 pigs/trt; 18 pigs/pen on slatted concrete floors). A source of ractopamine hydrochloride (10 mg/kg) was fed the last 28 d of the trial to induce increased growth rate. Measurements included gait scoring (0-4; GS ≥ 2 defined as lame) and serum and saliva bone synthesis (osteocalcin), bone degradation (CTX1) and cartilage synthesis (P2CP), and cartilage degradative biomarkers (CTX2, C2C) and synthesis:degradation ratios measured at baseline, d 7, d 36 and d 70. Individual biomarkers were logarithmically transformed (base 10). Proc Mixed GLM procedure of SAS was performed on log-transformed data and means were determined using LSD test. Nonparametric comparisons (% lameness) were tested using Chi-squared analysis. A P-value &amp;lt; 0.05 was considered significant and P ≤ 0.10, a trend. As shown in Table, 1, lameness incidence was greatest for pigs fed ITM and OTM glycinate which was greater than OTM complex and MMHAC (P = 0.10). In general, there was good agreement between serum and saliva biomarkers, with pigs fed MMHAC having the greatest serum bone synthesis biomarker (osteocalcin) which differed from pigs fed OTM complex (P &amp;lt; 0.05). Cartilage synthesis concentrations (P2CP (serum and saliva); and P2CP/C2C and P2CP/CTX2 ratios (saliva) were also greatest for pigs fed MMHAC trace minerals (P &amp;lt; 0.05). Neither bone nor cartilage biomarkers were different between pigs fed ITM and OTM complex or glycinate. Osteocalcin was 10-fold less in saliva compared with serum. No treatment differences were observed in saliva for bone synthesis. The results demonstrated trace mineral source matters with respect to structural health. Significant differences between OTM sources were observed with MMHAC resulting in the highest bone and cartilage synthesis biomarker concentrations in serum and highest biomarkers for cartilage synthesis and synthesis:degradation ratios in saliva. Saliva appears to be a sensitive medium for measuring joint health biomarkers.

The Impact of Physiotherapy in the Management of Non-Operated Gonarthrosis in Mali

Introduction: According to the WHO, osteoarthritis is the result of mechanical and biological phenomena that destabilise the balance between the synthesis and degradation of cartilage and subchondral bone. Gonarthrosis is a genuine public health problem in developed countries due to its high frequency, the functional impotence it causes and its socio-economic impact [2, 3]. Its prevalence is estimated at between 7% and 17% in people aged over 45 [4]. This incidence has continued to increase over the last few decades due to the industrialisation of the world and the sedentary lifestyle of human beings. In the absence of any study on the role of physiotherapy in the management of gonarthrosis in Mali. We deemed it necessary to undertake a study whose aim was to evaluate the impact of physiotherapy in the management of non-operated gonarthrosis in the physiotherapy department of the Centre National d'Appareillage Orthopédique du Mali (C.N.A.O.M). Methods and Patients: This was a descriptive cross-sectional study over a period of one month. All patients seen in consultation with gonarthrosis and consenting were included. Results: In total, out of 561 patients seen in consultation at the C.N.A.O.M, we included 10 patients, i.e. 1.78%. Females accounted for 86%, with an average age of 55 years. Gonarthrosis was unilateral in 28.6% and bilateral in 71.4%. With the exception of one patient, all the other patients were overweight or obese. Apart from one patient, physiotherapy improved the symptoms in all our patients. Conclusion: Gonarthrosis is a very disabling condition. Our results are similar to those in the literature, i.e. it mainly affects obese adult women. Management is multidisciplinary. Physiotherapy plays a key role in the management of gonarthrosis. It significantly improves the clinical signs and quality of life of patients. A multicentre case-control study would be useful to assess the efficacy of physiotherapy alone in the management of gonarthrosis.

Comparison of growth factors isolated from exosomes present in maternal blood of cleft and non-cleft infants for identification and quantification of growth factors involved in the growth and development of cartilage.

Background: Cleft lip and palate (C.L.P.) is a common congenital condition which affects the orofacial region. The aetiology of C.L.P. is multifaceted and involves genetic and environmental factors that impact the shape and position of the nasal cartilage, resulting in an asymmetrical appearance of the nose. Growth factors are crucial in regulating cartilage synthesis and repair. Exosomes have emerged as a promising cell-free drug delivery system that facilitates intercellular communication and maintains tissue homeostasis. This study identifies and quantifies the growth factors present in exosomes derived from lactating maternal blood of cleft and non-cleft infants and compares them to evaluate the differences. The study aims to assess the potential of these exosomes as a therapeutic approach for C.L.P. management. Methods: Blood samples were collected from lactating mothers at Sharad Pawar Dental College and isolating plasma using centrifugation. Exosome and total protein isolation will be conducted in the laboratory, and immunoblotting will evaluate growth factors. Quantitative and comparative protein and growth factor analysis will be conducted separately for maternal blood samples. Results: The growth factors responsible for cartilage growth and development will be present in maternal exosomes, potentially leading to novel therapies for C.L.P. management. The study aims to demonstrate the therapeutic potential of exosomes, as carriers of intra-cellular factors, in transporting growth factors to the required site for managing C.L.P. Conclusions: Overall, by understanding the roles played by growth factors, intercellular communication, and genetic and environmental factors in the aetiology of C.L.P., this research can contribute to creating effective treatment strategies for C.L.P. management. Finding growth factors in exosomes made from the blood of nursing mothers could be a cutting-edge therapeutic strategy for treating C.L.P.

11 Extra-label bisphosphonate effects on cartilage turnover in juvenile horses challenged with intra-articular lipopolysaccharide

Perceived chondroprotective benefits of extra-label bisphosphonates, such as clodronate disodium (CD), in juvenile horses led to widespread use despite little scientific understanding of intra-articular impacts. The objective was to determine the effects of CD on articular cartilage hypothesizing that administration of CD would decrease cartilage degradation following an acute inflammatory challenge by lipopolysaccharide (LPS). To test this, 32 yearling Quarter Horses were stratified by age (500 ± 13 d), BW (336 ± 26 kg), sex (n = 16 female; n = 16 male) and initial bone optical density into 4 treatment groups. The 140-d study consisted of 2 phases: phase 1 (d 0–83) emulated sales prep and phase 2 (d 84–140) mimicked early performance training. Horses were housed individually (3.6 m × 7.3 m) and fed to meet exercise requirements. Treatments consisted of control (CON; n = 8), single-dose (1X; n = 8; d 84), 2-doses (2X; n = 8; d 0, 84), and 4-doses (4X; n = 8; d 0, 42, 84, 126). All horses received iso-volumetric intramuscular injections of 1.8mg/kg BW clodronate disodium (OSPHOS®) or saline (placebo) on d 0, 42, 84, and 126. Post treatment administration on d 126, radial carpal joints of each horse were injected with 0.8 mL of either 0.5 ng sterile LPS derived from Escherichia coli O55:B5 or sterile lactated Ringer's solution as a contralateral control. Synovial fluid was collected before LPS injection(h 0) and at 6, 12, 24, and 336 h post induction. Carpal circumference (CC), heart rate (HR), respiration rate (RR), and rectal temperature (RT) were recorded before each collection. Synovial fluid was analyzed for carboxypropeptide of type II collagen (CPII) and collagenase cleavage neopeptide (C2C) by ELISA. Data were analyzed using PROC MIXED of SAS. Treatment had no effect on HR, RR, or RT. As expected, intra-articular LPS increased CC, CPII, C2C, and CPII:C2C (P ≤ 0.01). There was a trend for a treatment effect for CC (P = 0.09) where CC was greater in 2X and 4X compared with 1X with CON being intermediate. There tended to be a treatment by hour interaction in CPII (P = 0.06) where CPII was greater in 4X and 2X compared with 1X and CON at h 24 and 336. Likewise,there was a trend for a treatment effect onCPII:C2C (P = 0.06) with 2X and 4X having greater synthesis:degradation than 1X and CON. In conclusion, LPS administration resulted in an expected increase in carpal circumference. Trends of increasing CPII and CPII:C2C in the 2X and 4X treatment group indicate a net increase in articular cartilage synthesis following 2–4 doses of CD despite larger CC, suggesting a greater inflammatory response.

Concentrations of dexmedetomidine and effect on biomarkers of cartilage toxicity following intra-articular administration in horses

The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. 12 research horses. Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration using immunoassays. Plasma concentrations of dexmedetomidine fell below the limit of quantification (LOQ) (0.005 ng/mL) by 2.5 and 8 hours postadministration of 1 and 5 μg/kg, respectively. Synovial fluid concentrations were above the LOQ (0.1 ng/mL) of the assay at 24 hours in both dose groups. Drug was not detected in urine samples at any time postdrug administration. CS846 concentrations were significantly decreased relative to baseline at 12 hours postadministration in the saline group and significantly increased in the 5-μg/kg-dose group at 24 hours. Concentrations of C2C were significantly decreased at 12 and 24 hours postadministration in the saline treatment group. There were no significant differences in CS846 or C2C concentrations between dose groups at any time. Systemic concentrations of dexmedetomidine remained low, compared to synovial fluid concentrations. CS846, a marker of articular cartilage synthesis, increased in a dose-dependent fashion. Based on these findings, further dose titration and investigation of analgesic and adverse effects are warranted.

Chondrogenic differentiation of mouse CD105+ stem/progenitor cells on amino-group-functionalized biosilica-hydrogel scaffolds

Mesenchymal stem/progenitor cells (MSPCs) are critical for tissue regeneration. Moreover, the CD105 antigen identifies early MSPCs with increased chondrogenic differentiation ability. We hypothesized that amine-(NH2)-functionalized biosilica incorporating hydrogel scaffolds, seeded with mCoSPCs105+ would contribute to creating tissue-engineered scaffolds, capable of de novo cartilage synthesis. Scaffolds were characterized by water uptake, lysozyme degradation, axial compression, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Differentiation stimulus of scaffold functionalization was evaluated using Alcian blue staining. Cartilage-forming abilities of mCoSPCs105+ were evaluated using Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Biosilica particle incorporation into scaffolds resulted in increased water uptake capacity and compression force withstanding abilities. Amine-(NH2)-group functionalization of biosilica led to significantly increased stem cell differentiation potential, by Alcian blue staining, in the first 3 weeks. Scaffold attachment and viable cell proliferation were observed for 6 weeks under chondrogenic differentiation. Downregulation of Runx2, an increase of Col10a1, Ihh, and maintenance of Sox9, was seen under these culture conditions. mCoSPCs105+ gene expression pattern was defined by the significant upregulation of Col1a1, Col2a1, Prg4, and Agc-1 over 6 weeks of incubation compared to the unsorted control. Immunostaining of cell-seeded scaffolds revealed significantly higher secretion of proteins relevant to cartilage extracellular matrix. The preselecting of CD105+ phenotype in MSPCs may enhance tissue regeneration of fibrocartilage and biosilica nanoparticles may be a beneficial additive in tissue engineering of scaffolds.

Omega-3 Fatty Acids for the Management of Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is a disease which results in degeneration of cartilage within joints and affects approximately 13.6% of adults over 20 years of age in Canada and the United States of America. OA is characterized by a state of low-grade inflammation which leads to a greater state of cellular catabolism disrupting the homeostasis of cartilage synthesis and degradation. Omega-3 polyunsaturated fatty acids (PUFAs) have been postulated as a potential therapeutic treatment option for individuals with OA. Omega-3 PUFAs are recognized for their anti-inflammatory properties, which could be beneficial in the context of OA to moderate pro-inflammatory markers and cartilage loss. The purpose of this narrative review is to outline recent pre-clinical and clinical evidence for the use of omega-3 in the management of OA.