scholarly journals Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study

2019 ◽  
Vol 8 (7) ◽  
pp. 975 ◽  
Author(s):  
Paola De Luca ◽  
Alessandra Colombini ◽  
Giulia Carimati ◽  
Michelangelo Beggio ◽  
Laura de Girolamo ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Type I Collagen ◽  
Fibrous Tissue ◽  
Type I ◽  
Collagen Deposition ◽  
Symptomatic Knee Osteoarthritis ◽  
In Vitro Investigation ◽  
Symptomatic Knee ◽  
Retrospective Clinical Study

Among all joints affected, knee osteoarthritis has a prevalence of about 10% in men and 13% in women over 60 years old. Knee osteoarthritis has high economic and social costs and may have a devastating impact on patient quality of life. Treatment of symptomatic knee Osteoarthritis may involve oral or topical administration of non-steroidal anti-inflammatory drugs or intra-articular injection of corticosteroids. Recently, a novel injectable collagen formulation (ChondroGrid) consisting of bovine hydrolyzed <3 kDa type I collagen has been developed and is currently available on the market as an injectable medical device. The primary objective of this study was to investigate the in vitro and in vivo effects of ChondroGrid in treating knee osteoarthritis symptoms to assess its safety and performance. Viability and proliferation of ChondroGrid-exposed human chondrocytes derived from five donors were assessed through the Alamar Blue/CyQuant assays. Their expression of MMP1/MMP3 and TIMP1/TIMP3 was then assessed through RT-PCR and that of TGFβ1, IGF-I, and VEGF using ELISA assays. Shape and ECM deposition were assessed using the Bern score after a 28-day ChondroGrid exposure, and collagen deposition was assessed using immunostaining. Records of 20 patients affected by Kellgren Lawrence grade 1 to 4 knee osteoarthritis who received three 4mg/2mL ChondroGrid injections 2 weeks apart were then retrospectively assessed to compare VAS, Lequesne, and WOMAC scores collected before and 15, 45, and 225 days after the first injection. ChondroGrid had no effects on the markers under consideration, but induced type-II and inhibited type-I collagen deposition; the Bern score was higher when cells were cultured with ChondroGrid. Patients experienced a 44% Lequesne score and a 55% VAS at moving score reduction. All other scores decreased >70%. ChondroGrid may prompt chondrocytes to produce hyaline cartilage, prevent fibrous tissue formation, and be a safe and effective adjuvant to treat symptomatic knee osteoarthritis.

scholarly journals Polymerized-Type I Collagen Downregulates Inflammation and Improves Clinical Outcomes in Patients with Symptomatic Knee Osteoarthritis Following Arthroscopic Lavage: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Janette Furuzawa-Carballeda ◽  
Guadalupe Lima ◽  
Luis Llorente ◽  
Carlos Nuñez-Álvarez ◽  
Blanca H. Ruiz-Ordaz ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Clinical Outcomes ◽  
Type I Collagen ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Lequesne Index ◽  
Arthroscopic Lavage ◽  
Symptomatic Knee Osteoarthritis ◽  
Symptomatic Knee ◽  
Urinary Levels

Objectives. Polymerized-type I collagen (polymerized collagen) is a downmodulator of inflammation and cartilage regenerator biodrug.Aim. To evaluate the effect of intraarticular injections of polymerized collagen after arthroscopic lavage on inflammation and clinical improvement in patients with knee osteoarthritis (OA).Methods. Patients (n=19) were treated with 6 intraarticular injections of 2 mL of polymerized collagen (n=10) or 2 mL of placebo (n=9) during 3 months. Followup was 3 months. The primary endpoints included Lequesne index, pain on a visual analogue scale (VAS), WOMAC, analgesic usage, the number of Tregs and proinflammatory/anti-inflammatory cytokine-expressing peripheral cells. Secondary outcomes were Likert score and drug evaluation. Clinical and immunological improvement was determined if the decrease in pain exceeds 20 mm on a VAS, 20% of clinical outcomes, and inflammatory parameters from baseline. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTXII) and erythrocyte sedimentation rate (ESR) were determined.Results. Polymerized collagen was safe and well tolerated. Patients had a statistically significant improvement (P<0.05) from baseline versus polymerized collagen and versus placebo at 6 months on Lequesne index, VAS, ESR, Tregs IL-1β, and IL-10 peripheral-expressing cells. Urinary levels of CTXII were decreased 44% in polymerized collagen versus placebo. No differences were found on incidence of adverse events between groups.Conclusion. Polymerized collagen is safe and effective on downregulation of inflammation in patients with knee OA.

scholarly journals Long-Term Effectiveness of Polymerized-Type I Collagen Intra-Articular Injections in Patients with Symptomatic Knee Osteoarthritis: Clinical and Radiographic Evaluation in a Cohort Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Adrián Borja-Flores ◽  
Salvador I. Macías-Hernández ◽  
Gabriela Hernández-Molina ◽  
Andric Perez-Ortiz ◽  
Eloy Reyes-Martínez ◽  
...  
Keyword(s):  
Cohort Study ◽  
Knee Osteoarthritis ◽  
Therapeutic Effect ◽  
Type I Collagen ◽  
Joint Space Width ◽  
Joint Space ◽  
Type I ◽  
Replacement Surgery ◽  
Symptomatic Knee Osteoarthritis ◽  
Symptomatic Knee

Objective. Polymerized-type I collagen (polymerized-collagen) is a downregulator of inflammation and a tissue regenerator. The aim was to evaluate the effect of intra-articular injections (IAIs) of polymerized-collagen among patients with symptomatic knee osteoarthritis (OA) in delaying or preventing joint replacement surgery. Patients and Methods. This was a cohort study of 309 patients with knee OA. Patients with mild-to-moderate disease were treated weekly with IAIs of 2 mL of polymerized-collagen for six weeks (n = 309). Follow-up was for 6–60 months. The primary endpoints included the following determinations: (1) therapeutic effect; (2) survival from total knee replacement surgery (TKR); (3) Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and pain (visual analogue scale, VAS). Clinical improvement was defined as a decrease in pain exceeding 20 mm on the VAS and the achievement of at least 20% improvement from baseline with respect to the WOMAC score. Radiographic analysis was performed at baseline and 60 months. The joint space width in the medial, lateral, and patellofemoral compartments was calculated. Results. Patients who received IAIs of polymerized-collagen had a statistically significant improvement in the primary criteria (p<0.05). Kaplan–Meier survival analysis of the therapeutic effect demonstrated 98.8% survival at 60 months with TKR as the endpoint. There was no significant reduction in joint space in any compartment based on the analyzed radiographs. No serious adverse events were recorded. Conclusion. Polymerized-collagen increased the time to TKR by at least 60 months, modifying the disease course, improving functional disability, and decreasing pain.

Effect of MMP-13 degraded SPARC on type I collagen and its biomarker potential in colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 717-717
Author(s):  
Stephanie Nina Kehlet ◽  
Henrik Harling ◽  
Lars N Jørgensen ◽  
Morten A Karsdal ◽  
Nicholas Willumsen
Keyword(s):  
Colorectal Cancer ◽  
Type I Collagen ◽  
Collagen Degradation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matricellular Protein ◽  
Elisa Assay ◽  
Type I ◽  
Healthy Controls ◽  
Collagen Deposition

717 Background: Increased collagen deposition and remodeling of the extracellular matrix has been shown to play a role in the pathology of gastrointestinal cancer (GC). The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) binds collagens and hereby regulates collagen fibrillogenesis. Matrix metalloproteinase (MMP) mediated cleavage of SPARC, increases the affinity for collagens up to 20-fold. SPARC has been shown to be overexpressed in GC patients and associated with GC cell invasion and metastasis. Increased expression and cleavage of SPARC might therefore be implicated in GC pathology by increasing collagen deposition. Here, we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) quantifying a specific MMP-13 generated fragment of SPARC - a cleavage site involved in increased collagen affinity. The biomarker potential of this fragment was examined in serum from colorectal cancer (CRC) patients and healthy controls. Moreover, we evaluated the ability of cleaved SPARC to prevent type I collagen degradation in vitro. Methods: A monoclonal antibody was raised against a MMP-13-generated neo-epitope of SPARC and a competitive ELISA assay (SPARC-M) was developed and technically validated. Serum levels were assessed in CRC patients (n=50) and healthy controls (n=30). The ability of cleaved SPARC to prevent collagen degradation was investigated using an ELISA assay measuring type I collagen degradation by MMP-9. Results: SPARC-M was technically robust and specific for SPARC cleaved by MMP-13. The fragment was elevated in CRC patients when compared to healthy controls (p=0.0097). When MMP-13 degraded SPARC was incubated with type I collagen and MMP-9, type I collagen degradation was completely inhibited suggesting that SPARC increases collagen deposition by preventing collagen degradation. Conclusions: SPARC-M was significantly elevated in CRC patients compared to healthy controls suggesting biomarker potential. Biologically, cleaved SPARC may prevent type I collagen degradation hereby leading to a pro-tumorigenic environment. Larger clinical studies are needed to validate the clinical use of this biomarker in GC.

scholarly journals Matrix metalloproteinase 14 is required for fibrous tissue expansion

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Susan H Taylor ◽  
Ching-Yan Chloé Yeung ◽  
Nicholas S Kalson ◽  
Yinhui Lu ◽  
Paola Zigrino ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Collagen Fibril ◽  
Type I Collagen ◽  
Fibrous Tissue ◽  
Tissue Expansion ◽  
Collagen Fibrils ◽  
Collagen I ◽  
Type I ◽  
Tendon Development

Type I collagen-containing fibrils are major structural components of the extracellular matrix of vertebrate tissues, especially tendon, but how they are formed is not fully understood. MMP14 is a potent pericellular collagenase that can cleave type I collagen in vitro. In this study, we show that tendon development is arrested in Scleraxis-Cre::Mmp14 lox/lox mice that are unable to release collagen fibrils from plasma membrane fibripositors. In contrast to its role in collagen turnover in adult tissue, MMP14 promotes embryonic tissue formation by releasing collagen fibrils from the cell surface. Notably, the tendons grow to normal size and collagen fibril release from fibripositors occurs in Col-r/r mice that have a mutated collagen-I that is uncleavable by MMPs. Furthermore, fibronectin (not collagen-I) accumulates in the tendons of Mmp14-null mice. We propose a model for cell-regulated collagen fibril assembly during tendon development in which MMP14 cleaves a molecular bridge tethering collagen fibrils to the plasma membrane of fibripositors.

Collagen fibrillogenesis in vitro: interaction of types I and V collagen

1986 ◽  
Vol 44 ◽  
pp. 210-211
Author(s):  
Arthur J. Wasserman ◽  
Kathy C. Kloos ◽  
David E. Birk
Keyword(s):  
Type I Collagen ◽  
Corneal Stroma ◽  
Minor Component ◽  
Homogeneous Distribution ◽  
Type I ◽  
Type V Collagen ◽  
Fibril Morphology ◽  
Type V ◽  
In Vitro Interaction

Type I collagen is the predominant collagen in the cornea with type V collagen being a quantitatively minor component. However, the content of type V collagen (10-20%) in the cornea is high when compared to other tissues containing predominantly type I collagen. The corneal stroma has a homogeneous distribution of these two collagens, however, immunochemical localization of type V collagen requires the disruption of type I collagen structure. This indicates that these collagens may be arranged as heterpolymeric fibrils. This arrangement may be responsible for the control of fibril diameter necessary for corneal transparency. The purpose of this work is to study the in vitro assembly of collagen type V and to determine whether the interactions of these collagens influence fibril morphology.

THE EFFECT OF A TRIPOD CANE ON THE FUNCTIONAL MOBILITY OF PATIENTS WITH KNEE OSTEOARTHRITIS

2020 ◽  
Vol 5 (1) ◽  
pp. 29
Author(s):  
Nelson Sudiyono
Keyword(s):  
Knee Osteoarthritis ◽  
Cross Sectional Study ◽  
Functional Mobility ◽  
Cross Sectional ◽  
Knee Oa ◽  
Walking Aids ◽  
Symptomatic Knee Osteoarthritis ◽  
Symptomatic Knee ◽  
Contralateral Hand ◽  
Painful Knee

Background: Canes have been recommended as walking aids for knee osteoarthritis to reduce the loading on the affected knee. Patients are usually recommended to hold the cane in the contralateral hand to the affected knee. Nevertheless, some patients prefer to hold the cane ipsilateral to the affected knee. However, the effect of using ipsilateral or contralateral tripod cane on functional mobility in patients with knee osteoarthritis is still unknown Objective: To compare the immediate effect of ipsilateral and contralateral tripod cane usage on functional mobility in patients with symptomatic knee osteoarthritis Method: This cross-sectional study involved 30 overweight or obese patients with symptomatic unilateral or bilateral knee osteoarthritis (Kellgren Lawrence grade 2 and 3) who never use a cane. Functional mobility was evaluated with Time Up and Go test in three conditions; without walking aid, with tripod cane contralateral and ipsilateral to the more painful knee. Results: The TUG time of aid-free walking is 4.75 (p < 0.001, 95% CI 3.79 - 5.71) seconds faster than ipsilateral cane use and 6.69 (p < 0.001, 95%CI 5.35 - 8.03) seconds faster than contralateral cane use. The TUG time of ipsilateral cane use is 1,94 (95% CI, 1.13 - 2.79) seconds faster than contralateral. Conclusion: Patients with symptomatic knee OA who use tripod cane ipsilateral to the more painful knee have higher functional mobility than the contralateral.

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