Collagen Breakdown Research Articles

Superovulation alters the expression of endometrial genes critical to tissue remodeling and placentation.

Epidemiologic data suggest that in vitro fertilization (IVF) is associated with an increased risk of disorders of placentation including preeclampsia and fetal growth restriction. Specifically, studies have demonstrated that singleton pregnancies conceived following a fresh embryo transfer are at an increased risk of delivering an infant with low birth weight compared to those conceived following a frozen embryo transfer. The mechanism responsible for this association remains unclear. Procedures utilized in IVF have also been linked with epigenetic changes and gene expression changes in both fetal and maternal tissues. Data suggest that modifications in the maternal endometrium can lead to disordered trophoblast invasion and placentation. This study examines the effect of ovarian stimulation on endometrial gene expression and DNA methylation during the window of implantation to examine potential pathways playing a role in the adverse outcomes associated with IVF. Endometrial biopsies were obtained from oocyte donors and age-matched naturally cycling women 11days following oocyte retrieval in donors or 12days following luteinizing hormone (LH) surge in naturally cycling women. Global gene expression was analyzed via Affymetrix Human Gene 1.1 ST array and confirmed with RT-qPCR. DNA methylation was assessed with the Infinium DNA methylation 450K BeadChip. Analysis of endometrial gene expression from 23 women (11 oocyte donors and 12 controls) demonstrated 165 genes with a greater than twofold change in expression between donors and controls. While there were 785 genes with significant differential methylation in the endometrium of donors when compared with control subjects, none of the genes with altered expression showed significant changes in DNA methylation. Analysis of the differentially expressed genes showed enrichment for genes involved in endometrial remodeling including PLAT, HSPE2, MMP2, and TIMP1. Validation studies using RT-qPCR found a 73% reduction in expression of heparanase 2 (HSPE2) an enzyme associated with both angiogenesis and cell invasion, a greater than twofold increase in tissue-type plasminogen activator (PLAT), a serine protease participating in matrix degradation, and a 70% increase in MMP2, a gelatinase involved in collagen and fibronectin breakdown. Superovulation alters expression of genes critical to endometrial remodeling during early implantation. Such changes could lead to altered trophoblast migration and impaired endovascular invasion. These findings offer a potential mechanism for the adverse perinatal outcomes observed following embryo transfer during fresh IVF cycles.

Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery.

Collagen and hyaluronan are the most abundant components of the extracellular matrix (ECM) and their overexpression in tumors is linked to increased tumor growth and metastasis. These ECM components contribute to a protective tumor microenvironment by supporting a high interstitial fluid pressure and creating a tortuous setting for the convection and diffusion of chemotherapeutic small molecules, antibodies, and nanoparticles in the tumor interstitial space. This review focuses on the research efforts to deplete extracellular collagen with collagenases to normalize the tumor microenvironment. Although collagen synthesis inhibitors are in clinical development, the use of collagenases is contentious and clinically untested in cancer patients. Pretreatment of murine tumors with collagenases increased drug uptake and diffusion 2-10-fold. This modest improvement resulted in decreased tumor growth, but the benefits of collagenase treatment are confounded by risks of toxicity from collagen breakdown in healthy tissues. In this review, we evaluate the published in vitro and in vivo benefits and limitations of collagenase treatment to improve drug delivery.

Quantitative proteomics identify an association between extracellular matrix degradation and immunopathology of genotype VII Newcastle disease virus in the spleen in chickens

Pathogenesis of genotype VII Newcastle disease virus (NDV) is characterized with remarkable immunopathology in the spleen in chickens. However, the mechanism for this unique pathological phenotype is not fully understood. Previous transcriptomics data showed that genotype VII NDV JS5/05 caused a greater downregulation of extracellular matrix (ECM) genes than genotype IV virus Herts/33 in the spleen. In this study, the role of ECM in pathology of genotype VII NDV was investigated using quantitative proteomics. Pathology studies showed that JS5/05 caused severe immunopathology characterized with remarkable necrosis in the spleen, whereas Herts/33 only induced mild pathological changes. The ECM was firstly enriched from the spleens and ECM proteins of different categories were identified by LC-MS/MS. Quantitative proteomic analysis showed that JS5/05 caused a significant disruption of ECM integrity and molecular composition compared to Herts/33. Particularly, JS5/05 induced a more remarkable collagen breakdown in the spleen compared to Herts/33. Moreover, matrix metalloproteinase (MMP)-13 and -14 were significantly upregulated by JS5/05 infection. KEGG pathway analysis suggested that differential regulation of ECM proteins by JS5/05 and Herts/33 may impact pathology through different pathways. Therefore, our results suggested that MMP upregulation and consequent ECM degradation contribute to immunopathology of genotype VII NDV in the spleen. SignificancePathogenesis of genotype VII NDV is characterized with severe immunopathology in the spleen in chickens. Elucidating the mechanism of this pathology phenotype is critical to understand pathogenesis of genotype VII NDV. Here, we present the proteomic data of an important non-cellular compartment, the extracellular matrix (ECM), in the spleen from chickens infected with genotype VII and IV NDVs. Our results suggest that significant upregulation of matrix metalloproteinases by genotype VII NDV and consequent disruption of ECM integrity and composition may be associated with immunopathology in the spleen. Moreover, ECM degradation, represented by collagen breakdown, is an important pathology event in the process of genotype VII NDV infection. Our study for the first time presents evidence of ECM regulation by NDV and adds ECM remodeling as a new manifestation for NDV pathology. Our findings also deepen the understanding of NDV pathogenesis.

FUNCTIONAL ACTIVITY OF THROMBOCYTOSIS HEMOSTASIS SECTION IN EXPERIMENTAL MODELING OF GINGIVITE AND ALVEOLITES

The aim of the study was to study the functional activity of platelet hemostasis in the experimental modeling of gingivitis and alveolitis.Materials and methods. The study was carried out on non-linear laboratory white male rats weighing 240.0 ± 30.0 g divided into four groups: experimental gingivitis, alveolitis and two groups of intact control by examination of platelet aggregation, determination of total, free and bound hydroxyproline in the urine, morphological verification of changes in the bone tissue of periodontal rats.Results. Aggregation activity of platelets with a low concentration of inducer ADP in the alveolitis increases the degree and rate of aggregation. High concentrations of ADP do not cause changes in platelet aggregation. Changes in all levels of hydroxyproline in the urine of rats indicate the breakdown of collagen to varying degrees, depending on the pathology.Conclusions. Low concentrations (2.5 μmol / L) of adenosine diphosphate increase the functional activity of platelets. High concentrations (5.0 and 10.0 μmol / L) of adenosine diphosphate do not affect the functional activity of thrombocytes in animals with alveolitis. Changes in all levels of hydroxyproline in urine in rats, found in rats with gingivitis, and a decrease in free hydroxyproline in rats with alveolitis suggest a pronounced deceleration of collagen degradation in gingivitis and the onset of this process in animals with alveolitis.

CD40L promotes development of acute aortic dissection via induction of inflammation and impairment of endothelial cell function

Acute aortic dissection is one of the most lethal cardiovascular disease. The major histopathological feature of AAD is medial degradation, especially breakdown of elastin and collagen. However, the underlying mechanism remains a mystery. Platelets expressed CD40 Ligand (CD40L) is recently recognised as a key effector of cardiovascular disease development through its pro-inflammatory effect. To clarify the role of CD40L in AAD, we examined level of CD40L in human blood serum samples and found that it is significantly higher in AAD patients compared with healthy subjects (26.8±5.52 ng/mL versus 13.4±4.00 ng/mL). To further investigate if CD40L is involve in the development of AAD, we applied β-aminopropionitrile (BAPN) induced mouse model of AAD. Consistent with the human data, circulating CD40L in AAD mice much higher than normal mice (148.40±75.96 pg/mL versus 44.09±19.65 pg/mL). Meanwhile, multiple pro-inflammatory chemokines significantly increased in AAD mice. Importantly, the CD40L-/- mice treated with BAPN did not develop these phenotypes. Lastly, we confirmed that endothelial cells migration was significantly inhibited by CD40L, suggesting impaired recovery from intimal injury. In summary, we found that CD40L promoted AAD development through its pro-inflammatory effects and inhibition of endothelial cell function.

Muscle Damage Indicators after Land and Aquatic Plyometric Training Programmes

Plyometric training is an important part of athletic conditioning with many significant benefits, including improved motor abilities and performance, but it can also increase the serum indices of muscle damage, collagen breakdown, muscle swelling, and soreness. Due to the physical characteristics of water, plyometric training in water presents less eccentric contraction, facilitates faster transition from the eccentric to concentric phase of a jump and offers greater resistance during concentric contraction with acute lower indices of muscle damage. To advance our understanding of the long-term effects of an eight-week plyometric training programme on land and in water on muscle damage indicators (lactate dehydrogenase (LDH), creatine kinase (CK) and serum urea (SU)), two experimental groups of physically active men (a group on land (EG1) and a group in water (EG2)) were tested before and after the first and the last plyometric training to monitor muscle damage indicators and adaptations. The results showed changes in CK activity after both plyometric trainings for EG1 and only after the first training for EG2. Moreover, after the eight- week programme, significant difference was observed in CK activity in comparison with EG2. There were no observed changes in LDH activity while SU showed greater changes for the group on land. The plyometric training programme in water resulted in smaller levels of muscle damage indicators. Although both experimental groups conducted the same plyometric training with the same jump volume, the eccentric and concentric loads were not the same, so it can be concluded that adaptations in muscle damage processes are faster with smaller eccentric loads.

Time between anterior cruciate ligament injury and reconstruction and cartilage metabolism six-months following reconstruction

BackgroundTo determine the association between time from injury to ACL reconstruction (TimeInjury–ACLR) and biochemical markers of cartilage metabolism and inflammation six months following ACL reconstruction (ACLR). MethodsIndividuals with a unilateral ACL injury were enrolled at initial presentation in the orthopedic clinic; blood was collected six months following ACLR. Enzyme-linked immunosorbent assays were used to analyze the ratio of serum concentrations of type-II collagen breakdown (C2C) to synthesis (CPII), plasma matrix metalloproteinase-3 (MMP-3), interleukin-6 (IL-6), and serum aggrecan neoepitope (ARGS). We used separate linear regressions to assess associations between biochemical markers and TimeInjury–ACLR. ResultsTwenty-two participants (50% females, mean [SD], age 21.9 [4.5] years old; BMI 23.8 [2.6] kg/m2) completed the study. TimeInjury–ACLR ranged from nine to 67days (31.0 [14.4days]). Greater TimeInjury–ACLR predicted greater serum C2C:CPII ratios six months following ACLR (C2C:CPII=0.15 [0.02], R2=0.213, P=0.030). Males (R2=0.733, P=0.001) but not females (R2=0.030, P=0.609) demonstrated a significant association between greater C2C:CPII and TimeInjury–ACLR at the six-month follow-up exam. TimeInjury–ACLR did not associate with IL-6, MMP-3, or ARGS at six months. ConclusionsGreater time between injury and ACL reconstruction was associated with greater serum C2C:CPII six months following ACLR in males but not females, and IL-6, MMP-3, and ARGS levels were not associated with TimeInjury–ACLR in males or females. The time between ACL injury and ACLR may affect collagen metabolism in males and should be further investigated in a larger study along with other patient-relevant outcomes.

Labisia pumila prevented osteoarthritis cartilage degeneration by attenuating joint inflammation and collagen breakdown in postmenopausal rat model.

The tropical herb Labisia pumila is traditionally used in facilitating childbirth and post-partum care. The effects of L. pumila leaf extract (LP) in explant cartilage culture and on postmenopausal osteoarthritis (OA) rat model were assessed. The LP (10, 25 and 50µg/ml) or diclofenac (10µg/ml) was added to the cartilage explants containing bovine IL-1β (20ng/ml), to evaluate their direct effects on cartilage degradation. In the preclinical study, rats were grouped (n=8) into: non-treated OA; OA+diclofenac (5mg/kg); OA+LP extract (150 and 300mg/kg); and healthy control. To induce OA, monosodium iodoacetate was injected into the ovariectomised female rats' intra-articular knee joints and evaluated for OA severity after 8weeks via physical (radiological, macroscopic and histological observations), biochemical, ELISA and mRNA expression analysis (for inflammation and cartilage degradation biomarkers). The LP reduced the nitric oxide and proteoglycan release from the cartilage explants under IL-1β induction. The radiological, macroscopic, microscopic and histological images showed the OA rats treated with LP and diclofenac had significantly reduced osteophytes and cartilage erosions compared to non-treated OA rats. The extract significantly up-regulated the anti-inflammatory interleukin-10, collagen type II and down-regulated pro-inflammatory PTGS2 (prostaglandin-endoperoxide synthase 2) mRNA expressions compared to non-treated control. The LP treatment significantly reduced serum collagenases (MMP-1 and MMP-3) and collagen type II degradation biomarker (CTX-II) levels in OA rats. The LP containing myricetin and gallic acid suppressed inflammation, collagenases and cartilage degradation, and helped cartilage matrix synthesis, to prevent OA at the dose equivalent to 30-60mg/kg daily for humans.

Nutraceuticals: A Review.

Skin aging is continuously influenced by various internal and external factors such as the biologic progression of cells, ultraviolet (UV) radiation, tobacco, nutritional deficiencies, and hormonal imbalances that lead to the degradation of skin cells. Through the degradation of skin cells, free radicals and inflammation weaken repair mechanisms and result in collagen and elastic fiber breakdown. The appearance of aging skin is highlighted by skin roughness, wrinkling, pigmentation change, telangiectasias, loss of elasticity, and decreased firmness, all of which are accelerated by these internal and external factors. Throughout the years, nutraceuticals have been studied to delay and fight against these internal and external factors, many of which are found in foods and byproducts consumed naturally. The aim of this review is to aid dermatologists in understanding the mechanism of action of popular nutraceuticals and their possible efficacy in antiaging and skin health.

Evaluation of gingival crevicular fluid and peri-implant sulcus fluid levels of periostin: A preliminary report.

Periostin is a protein present in alveolar bone and periodontal ligament whose function is related to response to external forces. The aims of this study are to detect levels of periostin in peri-implant sulcular fluid (PISF) and gingival crevicular fluid (GCF) and to evaluate the relationship between periostin, pyridinoline cross-linked carboxyterminal telopeptide of Type I collagen (ICTP), and C-terminal cross-linked telopeptide of Type I collagen (CTX) levels and clinical inflammatory symptoms and duration of functional loading. The study population comprised nine women and four men with mean age 43.23 ± 12.48. Twenty "bone-level designed" dental implants (DIs) placed in molar or premolar sites, without any signs of peri-implant bone loss and with a restoration in function for at least 12 months, were included in the study with 20 contralateral natural teeth (NT) as controls. Clinical parameters and restoration dates of the implants were recorded. PISF, GCF, ICTP, CTX, and periostin levels were evaluated using enzyme-linked immunosorbent assay. ICTP, CTX, and periostin levels were similar between DI and NT groups. There were no statistically significant differences between PISF and GCF values. When implants were grouped as healthy (gingival index [GI]=0) and inflamed (GI≥0), ICTP levels and PISF volume were lower in healthy implants compared with the inflamed group. Both periostin and CTX levels were negatively correlated with functioning time, suggesting less bone remodeling around DIs at later stages of functioning. Findings of this study suggest collagen breakdown products may be used as markers to evaluate peri-implant metabolism.

Efficacy of Topical Coffee Paste to Collagen Density in Wistar Rats Incision Wound

Background :Collagen plays a very important role in humans at every stage of wound healing. Coffee contains many antioxidants that stimulate the formation of collagen dermis by increasing the production of Tissue Inhibitor of Matrix Metalloproteinas-1 in the dermis that serves to inhibit the breakdown of collagen. This study aims to determine the efficacy of topical pasta coffee to collagen density.
 Methods: Experimental Laboratories Study with pre and post test controlled group design research was undertaken from September to November 2017 at Animal House and Dyatnitalis Laboratory, Palembang. 30 male white rats of wistar strain were divided into 5 groups then performed 2 cm dermal incision and giving various concentration of coffee paste. On the day 0 and 5th after coffee paste, the percentage of collagen density is checked. The efficacy of coffee paste was analyzed by Paired T Test/Wilcoxon while the comparison of efficacy was analyzed by Independent T Test / Mann Whitney then continued with One Way ANOVA Test and Tukey test. Data analysis using SPSS version 18.0.
 Results: There was an average difference of percentage level of collagen density before and after vitamin C (p = 0,003), coffee paste 20% (p = 0,043), coffee paste 40% (p = 0,045) and coffee paste 80% (p = 0,011) . In addition, there was an average difference of percentage of collagen density between negative control group with positive control group and 40% coffee paste. From the results of Post Hoc test results showed that there was a difference of percentage of collagen density of negative control group with coffee paste group 40%.
 Conclusion: There is efficacy of topical coffee paste on collagen density in various concentrations where the highest increase of collagen density is 246,96% after coffee paste 40%.
 Keyword: Coffee Pasta, Collagen, Injured Incision, Vitamin C

Assessment of the Correlation between Serum Prolidase and Alpha-Fetoprotein Levels in Egyptian Patients with Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) accounts as the sixth most common neoplasm on a global scale and the third most lethal with >600,000 deaths per year worldwide. Despite regular surveillance to detect small HCC, HCC is often diagnosed at advanced stage, after the symptoms related to HCC have appeared, and the 5-year survival rate for patients is only 7%. If HCC could be diagnosed at an early stage, potentially curative option, such as resection, ablation, and transplantation may be considered. Prolidase is an important enzyme that cleaves the bonds of dipeptides containing proline (X-pro), and plays a vital role in collagen turnover, matrix remodeling and cell growth. Metastatic tumor cell produce enhanced number of proteases that enable them to penetrate basement membrane and extracellular matrix. Therefore, tumor progression might depend on the breakdown of collagen and other extracellular matrix proteins. Aim of the work: Assess the possible diagnostic role of serum prolidase compared to alpha- fetoprotein which is the slandered marker used for diagnosis of HCC. Methods: The study was conducted upon 90 subjects who were divided into three groups: group I included 40 patients with liver cirrhosis and hepatocellular carcinoma, group II included 40 patients with HCV related liver cirrhosis without HCC, group III had 10 healthy subjects as controls. Plasma prolidase was measured by Enzyme Linked Immunosorbent assay (ELISA) using recombinant human peptidase D/prolidase (PEPD) ELISA kit lot. Results: In this study, the serum levels of serum prolidase were highest in patients of group I with HCC compared to those with liver cirrhosis and the control groups. Also, prolidase values increased with tumor number, overall size but not with vascular invasion nor with BCLC. Conclusion: There was a direct significant correlation between serum prolidase level and serum AFP level in HCC patients. Serum prolidase levels directly correlated to the tumor number and overall size so it has a good prognostic value.

A cross sectional study of bone and cartilage biomarkers: correlation with structural damage in rheumatoid arthritis

ABSTRACTThe aim of our study was to assess the relationship between bone and cartilage remodeling biomarkers and joint damage in Rheumatoid Arthritis (RA), and to detect whether they have the capacity to predict the progression of joint disease assessment by computed tomography (CT) erosion score. We analyzed 65 female patients with established RA in our Rheumatology Department. Serum levels of bone and cartilage markers were measured: osteocalcin (OC), N-propeptide of type I collagen (PINP), collagen type I and II, C-telopeptide (CTX I, CTX-II) and cartilage oligomeric matrix protein (COMP). Radiography of both wrist and MCP joints were available. Two expert-readers independently scored articular damage and progression using the High-resolution low dose CT scan in a blinded fashion. 65 female patients with established RA with a median age of 44 years were included. The median disease-duration was two years and the median (Disease activity score) DAS 28 score at 4.46 [2.65–7.36]. The percentage of patient with low disease activity was 13.8%, while 55.4 and 30.8% for those with moderate and high disease activity respectively. The resorption bone markers were high in active versus non-active RA. Wrist and MCP erosion scores were also associated with RA activity. Our study shows that biomarkers of bone and cartilage collagen breakdown were related to specific joint erosion in RA and could predict subsequent radiographic damage in RA. Further larger scale longitudinal studies maybe needed to confirm our data.

Application of Bone Turnover Markers PICP and β-CTx in the Diagnosis and Treatment of Breast Cancer with Bone Metastases

This study is to investigate the application of the bone turnover markers type I procollagen carboxyterminal propeptide (PICP) and β-isomerized forms of type I collagen breakdown products (β-CTx) in the diagnosis and treatment of breast cancer with bone metastases. A total of 162 breast cancer patients were included in this study. There were 70 cases with bone metastasis (BM group) and 92 cases without bone metastasis (non-bone metastasis, NBM group). The levels of the bone turnover markers PICP and β-CTx were measured using Electro-Chemiluminescence Immunoassay to compare the difference between BM and NBM group, before and after treatments in the NBM group, and to analyse the relationship with therapeutic effects. The BM group had higher PICP and β-CTx levels than the NBM group and also higher in the non-luminal type group than the luminal type group, the differences were all statistically significant. However, no statistically significant differences were found among the pN0, pN1, pN2, and pN3 subgroups of the NBM group. Among the 70 cases of BM patient after 3 months of treatment, there were 48 cases that showed clinical benefits, with significantly reduced PICP and β-CTx levels (p = 0.02, p = 0.00, respectively), but 22 cases showed disease progression with elevated PICP and β-CTx levels (p = 0.01, p = 0.04, respectively). The bone turnover markers PICP and β-CTx have crucial value in the diagnosis and treatment efficacy evaluation for women of breast cancer with bone metastases.

Effect of Fruit Juice Drink Containing Collagen Polypeptides from Pacific cod ( Gadus macrocephalus )Skin on UV Irradiation-induced Skin Photoaging

The protective effect of cod-skin collagen peptide combining juice drink(CJD)on UV Irradiation-induced skin photoaging was investigated. Male ICR mice were randomly divided into five groups:normal group(NC),model group(MC),low dose CJD treatment group(CJD-L),medium dose CJD treatment group(CJD-M)and high dose CJD treatment group(CJD-H). The protective effect of CJD on photoaging was evaluated by clinical signs,histological morphology,content of water and hydroxyproline of UV-irradiation mice skin. The activities of total superoxide dismutase(T-SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and the level of malondialdehyde(MDA)in skin and serum were assessed to explore the pathway of protection of CJD on UV Irradiation-induced skin photoaging. Compared with the model group,the CJD-M and CJD-H groups significantly reduced water loss(p<0.05)and collagen breakdown of photoaging skin(p<0.01),significantly enhanced activity of T-SOD,CAT,GSH-Px and decreased levels of MDA in skin and serum(p<0.05). This study showed that collagen peptide drinks could protect skin against UV irradiation-induced photodamage,which could effectively prevent and delay photoaging.

Hypothermia Promotes Cell-Protective and Chondroprotective Effects After Blunt Cartilage Trauma

Background: Cryotherapy is routinely administered after sports injuries of synovial joints. Although positive clinical effects on periarticular swelling and pain have been described, the effects on the cell biological activities of cartilage and synovial cells remain largely unknown so far. Hypothesis: Local hypothermia alleviates synovial reactions and prevents chondrocyte death as well as cartilage destructive processes after blunt cartilage trauma. Study Design: Controlled laboratory study. Methods: Human cartilage explants were impacted by a drop-tower apparatus (0.59 J) and cultured at 24 hours or 7 days in different temperature conditions (2 hours [short term], 16 hours [medium term], or throughout [long term] at 27°C; afterwards or throughout at 37°C). Besides, isolated human fibroblast-like synoviocytes (FLS) were stimulated with traumatized cartilage conditioned medium and cultured as mentioned above up to 4 days. The effects of hypothermia were evaluated by cell viability, gene expression, type II collagen synthesis and cleavage, as well as the release of matrix metalloproteinase (MMP)–2, MMP-13, and interleukin 6 (IL-6). Results: Seven days after trauma, hypothermic treatment throughout improved cell viability (short term: 10.1% [P = .016]; medium term: 6% [P = .0362]; long term: 12.5% [P = .0039]). Short-term hypothermia attenuated the expression of catabolic MMP-13 (mRNA: –2.2-fold [P = .0119]; protein: –2-fold [P = .0238]). Whereas type II collagen synthesis (1.7-fold [P = .0227]) was increased after medium-term hypothermia, MMP-13 expression (mRNA: –30.8-fold [P = .0025]; protein: –10.3-fold [P < .0001]) and subsequent cleavage of type II collagen (–1.1-fold [P = .0489]) were inhibited. Long-term hypothermia further suppressed MMP release (pro–MMP-2: –3-fold [P = .0222]; active MMP-2: −5.2-fold [P = .0183]; MMP-13: −56-fold [P < .0001]) and type II collagen breakdown (–1.6-fold [P = .0036]). Four days after FLS stimulation, hypothermia significantly suppressed the gene expression of matrix-destructive enzymes after medium-term (MMP-3: –4.1-fold [P = .0211]) and long-term exposure (a disintegrin and metalloproteinase with thrombospondin motifs 4 [ADAMTS4]: –4.3-fold [P = .0045]; MMP-3: –25.8-fold [P = .014]; MMP-13: –122-fold [P = .0444]) and attenuated IL-6 expression by trend. Conclusion: After blunt cartilage trauma, initial hypothermia for only 2 hours and/or 16 hours induced significant cell-protective and chondroprotective effects and promoted the anabolic activity of chondrocytes, while the expression of matrix-destructive enzymes by stimulated FLS was attenuated by prolonged hypothermia. Clinical Relevance: The findings of this preliminary ex vivo investigation indicate that optimized cryotherapy management after cartilage trauma might prevent matrix-degenerative processes associated with the pathogenesis of posttraumatic osteoarthritis.

Aberrant Patterns of Key Epithelial Basement Membrane Components in Keratoconus.

In the cornea, the epithelial basement membrane (BM) plays an important role in maintaining corneal integrity and homeostasis. Aberrations in this vital structure are associated with several corneal pathologies including keratoconus. The aim of this study was to investigate the expression of key structural components of the epithelial BM in keratoconic corneas and to identify and describe any aberrant patterns. Immunohistochemical labeling of key BM components including fibronectin, laminin, and type IV and VII collagen was performed in healthy and keratoconic corneas. Clear changes in the BM components in the keratoconic corneas were seen with the key structural components either being absent or forming a discontinuous pattern. Another aberrant pattern, the expression of BM proteins, particularly fibronectin, laminin, and type IV collagen, in the anterior stroma of keratoconic corneas was also observed. These results indicate the activation of keratocytes into the fibroblast and myofibroblast wound phenotypes and the potential source of corneal scarring commonly observed in keratoconic corneas. Our data also support the hypothesis of dysregulated collagen synthesis and breakdown in the keratoconic cornea, in particular, the BM, and suggest a role for the BM in initiation and progression of keratoconus.

Clinical and radiographic periodontal parameters and release ofcollagen degradation biomarkers in naswar dippers.

The aim of the present study was to compare clinical periodontal parameters and to assess the release of C-telopeptides pyridinoline cross-links (ICTP) and C-terminal crosslinked telopeptide (CTX) from gingival collagen of naswar (NW) and non-naswar (control) dippers. Eighty-seven individuals (42 individuals consuming NW and 45 controls) were included. Clinical (plaque index, bleeding on probing, probing depth and clinical attachment loss) and radiographic (marginal bone loss) periodontal parameters were compared among NW and control groups. Gingival specimens were taken from subjects in NW and control groups, assessed for ICTP and CTX levels (using ELISA) and analyzed using micro-Raman spectroscopy. The significance of differences in periodontal parameters between the groups was determined using Kruskal-Wallis and Mann-Whitney U tests. The percent loss of dry mass over exposure time and the rate of release of ICTP and CTX from all groups were compared using the paired t-test to examine the effects of exposure time. Clinical and radiographic periodontal parameters were significantly higher in the NW group than the control group (P<.01). In the Raman spectrum, the strongest and sharpest band occurred at 1260cm-1 amongst NW users. A Raman band at Amide I was observed with slight shifts in wave numbers. The rate of ICTP and CTX release was significantly higher in subjects from the NW group compared with those from the control group (P<.05). Both factors, the type of groups and time, had a significant effect on release of ICTP and CTX (P<.05). Within the limits of the present study, it may be concluded that clinical and radiographic periodontal parameters were worse among subjects in the NW group than in those of the control group. There is a higher degree of collagen breakdown in the connective tissue of subjects in the NW group as a result of naswar usage.

S1P inhibits trophoblast-mediated collagen breakdown via a decrease in activation of MMP2; a potential mechanism for reduced invasiveness

S1P inhibits trophoblast-mediated collagen breakdown via a decrease in activation of MMP2; a potential mechanism for reduced invasiveness

Effect of hypercortisolism on bone mineral density and bone metabolism: A potential protective effect of adrenocorticotropic hormone in patients with Cushing's disease.

ObjectiveTo investigate the effects of Cushing’s disease (CD) and adrenal-dependent Cushing’s syndrome (ACS) on bone mineral density (BMD) and bone metabolism.MethodsData were retrospectively collected for 55 patients with hypercortisolism (CD, n = 34; ACS n = 21) from January 1997 to June 2014. BMD was examined in all patients, and bone turnover markers were tested in some patients. Healthy controls (n = 18) were also recruited.ResultsThe lumbar spine and femoral neck BMD were significantly lower in the ACS and CD groups than in the control group. Lumbar BMD was significantly lower in the ACS than CD group. The collagen breakdown product (CTX) concentrations were significantly higher while the osteocalcin and procollagen type I N-terminal propeptide (PINP) concentrations were significantly lower in the ACS and CD groups than in the control group. The PINP concentration was significantly lower while the CTX concentration was significantly higher in the ACS than CD group. In the CD group only, lumbar BMD and serum adrenocorticotropic hormone had a significant positive correlation.ConclusionsBone turnover markers indicated suppressed osteoblast and enhanced osteoclast activities. PINP and CTX changes might indicate bone mass deterioration. Adrenocorticotropic hormone might be protective for lumbar BMD in patients with CD.