Structure Of Hyaline Cartilage Research Articles

Tetracalcium Phosphate Biocement Hardened with a Mixture of Phytic Acid–Phytase in the Healing Process of Osteochondral Defects in Sheep

Hyaline articular cartilage has unique physiological, biological, and biomechanical properties with very limited self-healing ability, which makes the process of cartilage regeneration extremely difficult. Therefore, research is currently focused on finding new and potentially better treatment options. The main objective of this in vivo study was to evaluate a novel biocement CX consisting of tetracalcium phosphate–monetit biocement hardened with a phytic acid–phytase mixture for the regeneration of osteochondral defects in sheep. The results were compared with tetracalcium phosphate–monetit biocement with classic fast-setting cement systems and untreated defects. After 6 months, the animals were sacrificed, and the samples were evaluated using macroscopic and histologic methods as well as X-ray, CT, and MR-imaging techniques. In contrast to the formation of fibrous or fibrocartilaginous tissue on the untreated side, treatment with biocements resulted in the formation of tissue with a dominant hyaline cartilage structure, although fine fibres were present (p < 0.001). There were no signs of pathomorphological changes or inflammation. Continuous formation of subchondral bone and hyaline cartilage layers was present even though residual biocement was observed in the trabecular bone. We consider biocement CX to be highly biocompatible and suitable for the treatment of osteochondral defects.

Vaşak (Lynx lynx)’ta Larynx Kıkırdakları, Trachea ve Akciğerler Üzerine Makroanatomik ve Histolojik Bir Çalışma

In this study the larynx, trachea, and lungs of one 1.5-year-old adult female lynx (Lynx lynx) were examined. The macro anatomical and histological structure of the larynx cartilages, trachea, and lungs were tried to be revealed by dissection and measurements. It was determined that the trachea had 48 cartilage rings (cartilago trachealis) up to the bifurcatio trachealis, the diameters of which narrow as they approach the lungs. The total tracheal length was 172.36 mm. It was seen that the cross-section of the lynx trachea resembled a circle. The hyaline cartilage structure surrounding the trachea was determined. A muscle structure called musculus transversus trachea, which closes the open ends of this cartilage and surrounds the cartilage from the outside, was detected. It was determined that the trachea consisted of tunica mucosa, submucosa, and tunica adventitia layers. The pulmo sinister in the lynx lung consisted of two main lobes, lobus cranialis, and lobus caudalis. Lobus cranialis was also divided among itself as pars cranialis and pars caudalis. Pulmo dexter was divided into four main lobes as lobus cranialis, lobus medius, lobus caudalis, and lobus accessorius. It was determined that there was connective tissue capsule surrounding the lung, respiratory bronchioles, alveoli, intraalveolar septum, and abundant blood vessels. In intraalveolar septum; capillaries, erythrocytes were determined. Type I and type II pneumocytes were seen covering the alveolar surface. In addition, it was determined that there were macrophages in the alveolar sacs.

A morphological and stereological investigation on the tongue of the merlin

The study aimed to reveal the similarities and differences of the tongue of the merlin with other bird species. Merlin is the smallest bird of the Falconidae family and lives in America, the northern regions of Europe and Asia, the Middle East, and Central Asia. Since these species don’t have teeth, lips, and cheeks, the tongue fulfills significant functions related to nutrition, and it differs morphologically as a result of differences in eating habits. In this study, the tongues obtained from five adult merlin (falco columbarius) were examined by morphological and stereological methods. It was determined that the tongue of the merlin was thin, long, and rectangular, the front part was oval, W-shaped papilla linguales caudales were found between the body and root of the tongue. The average length of the tongue was 26.32 ± 1.38 mm, the width was 7.26 ± 0.32 mm, and the thickness was 1.58 ± 0.14 mm. The histology of the tongue showed that the dorsal and ventral surfaces are covered with keratinized multilayered squamous epithelium; there are taste buds in the epithelial layer, the number of taste buds is higher especially on the root of the tongue; and the presence of paraglossum, which is in the hyaline cartilage structure. The volume of the tongue was on an average of 374.2 ± 14.08 mm3.

Scanning electron microscopic and histological features of the oral cavity of the Egyptian tortoise (Testudo kleinmanni).

This investigation was led to depict the structural and functional adaptations of the oral cavity of herbivorous Egyptian tortoises using scanning electron and light microscopes. The SEM showed that the triangular papillary tongue possessed three conical papillary subtypes: the rectangular conical on the tip, the round conical on the rest of the dorsal lingual surface and the elongated conical on the caudal portion of the lingual wing. The presence of the serrated lips with their valves compensated for the absence of the teeth. The rostral part had a vomeronasal opening while the middle part had the choana, but the caudal part had numerous openings of the salivary glands. There are three palatine folds: a single median palatine fold, two peripheral palatine folds and the choanal fold. The current histological results show the keratinized dorsal lingual surface, in which the keratinized layer extended to cover the papillae. Two types of lingual glands, according to their position, are papillary superficial and deep lingual glands. Papillary or superficial glands open in the interpapillary spaces via narrow openings, while the deep glands are surrounded by well-developed muscles and open via wide openings on the dorsal lingual surface. An entoglossal cartilaginous structure of hyaline cartilage was found in the mid- and hindtongue, with numerous chondrocytes lodged within the lacunae. Our results conclude that the oral cavity of the herbivorous Egyptian tortoise was adapted to the dietary and vigorous demands of the Egyptian fauna.

Glycosaminoglycan, Antimicrobial Defence Molecule and Cytokine Appearance in Tracheal Hyaline Cartilage of Healthy Humans.

Hyaline cartilage is an important tracheal structure, yet little is known about its molecular composition, complicating investigation of pathologies and replacement options. Our aim was to research tracheal hyaline cartilage structure, protective tissue factors and variations in healthy humans. The tissue material was obtained from 10 cadavers obtained from the Riga Stradins University Institute of Anatomy and Anthropology archive. Tissues were stained with Bismarck brown and PAS for glycosaminoglycans, and immunohistochemistry was performed for HBD-2, HBD-3, HBD-4, IL-10 and LL-37. The slides were inspected by light microscopy and Spearman’s rank correlation coefficient was calculated. The extracellular matrix was positive across hyaline cartilage for PAS, yet Bismarck brown marked positive proliferation and growth zones. Numerous positive cells for both factors were found in all zones. All of the antimicrobial defence molecules and cytokines were found in a moderate number of cells, except in the mature cell zone with few positive cells. Spearman’s rank correlation coefficient revealed strong and moderate correlations between studied factors. Hyaline cartilage is a tracheal defence structure with a moderate number of antimicrobial defence protein and cytokine immunoreactive cells as well as numerous glycosaminoglycan positive cells. The extracellular matrix glycosaminoglycans provide structural scaffolding and intercellular signalling. The correlations between the studied factors confirm the synergistic activity of them.

Current Concepts in the Etiology and Pathogenesis of Pectus Excavatum in Humans-A Systematic Review.

Pectus excavatum (PE) is the most common deformity of the chest wall and is characterized by the posterior depression of the sternum and the lower costal cartilages. To date, the etiology of PE in humans remains enigmatic. Several etiologic hypotheses have been proposed over the past two centuries. However, most of them have been scientifically dismissed and now have only historic value. In this systematic review, we assess scientific publications of the past two centuries addressing the issue of the origin of PE in humans. We present and discuss the histologic, genetic, biomechanical, and experimental scientific achievements that contributed to the clarification of its etiology and pathogenesis. With no clear consensus over the exact mechanism, most recent studies agree that the primordial defect leading the deformation of the anterior chest wall in PE is related to the costal hyaline cartilage structure and function. Further studies on this subject must be carried out. Genetic studies seem to be the most promising way to understand the exact mechanism of PE’s origin and pathogenesis.

Development of a Two-Layer Porous Scaffold Based on Porcine Nasal Septal Cartilage for Orthopedics.

The aim of the study was to design a construct based on a nasal septal cartilage plate providing required cell differentiation in different layers to replace a deep osteochondral defect and develop an algorithm of chemical and physical effect sequence to create non-immunogenic two-layer porous structure with requisite elasto-mechanical properties.Materials and MethodsThe plates derived from porcine nasal septal hyaline cartilage covered by perichondrium were multi-stage treated including freezing, equilibrating in a hypotonic saline solution (type I specimens); trypsinization, point IR-laser effect, re-trypsinization (type II specimens); a stabilizing effect of crosslinking agents — glyceraldehyde/ribose in an acidic medium — washing (type III specimens).For all type specimens:there were established stability parameters (collagen denaturation temperature using a thermal analysis; and Young’s modulus using a mechanical analysis);there were determined morphological characteristics using light and polarization microscopy with classical staining and nonlinear optical microscopy in second-harmonic generation mode.ResultsThermal, mechanical, and morphological properties in type I specimens slightly differed from those of the initial nasoseptal system. A considerable part of cells had destroyed membranes.In type II specimens, thermal stability of collagen frame was significantly lower; Young’s modulus decreased more than fourfold compared to type I specimens. Collagen structure of hyaline cartilage appeared to be disarranged, although the morphological differences of the hyaline part and perichondrium preserved. The construct matrix was almost completely decellularized. Successive exposure to laser radiation and trypsin resulted in the formation of partial holes in the matrix, ~100 μm in diameter.In type III specimens, both the thermal stability of the collagen frame and Young’s modulus (E) increased. Glyceraldehyde was more effective than ribose, E having reached the value typical for intact hyaline cartilage. Collagen fibers in type III specimens were thicker than in type I and II specimens. The morphological differences of the hyaline part and perichondrium and partial holes were preserved.ConclusionDue to sequential treatment by salts, trypsin, IR-laser radiation, and nontoxic crosslinking agents, nasal septal cartilage plate forms porous acellular construction consisting of two layers formed by type I (from perichondrium) and type II (from hyaline part) collagen fibers. In the present construction, stability, mechanical properties, and size of the partial holes can be assigned for cell colonization. It enables to use the construction to replace articular cartilage defects.

Effect of BMP-2 Adherent to Resorbable Sutures on Cartilage Repair: A Rat Model of Xyphoid Process.

Meniscal tears are often seen in orthopedic practice. The current strategy for meniscal repair has only had limited success with a relatively high incidence of re-operative rate. This study evaluates the therapeutic effects of Bone morphogenetic protein-2 (BMP-2) soaked sutures for cartilage repair, using a rat model of xyphoid healing. Vicryl-resorbable sutures were presoaked in BMP-2 solutions prior to animal experimentation. Rat xyphoid process (an avascular hyaline cartilage structure) was surgically ruptured followed by repair procedures with regular suture or with sutures that were pre-soaked in BMP-2 solutions. In vitro assessment indicated that presoaking the Vicryl-resorbable sutures with 10 µg/mL BMP-2 resulted in a sustained amount of the growth factor release up to 7 days. Histological analysis suggested that application of this BMP-2 soaked suture on the rat xyphoid process model significantly improved the avascular cartilage healing compared to non-soaked control sutures. In conclusion, data here confirm that the rat xyphoid process repair is a reproducible and inexpensive animal model for meniscus and other cartilage repair. More importantly, coating of BMP-2 on sutures appears a potential avenue to improve cartilage repair and regeneration. Further study is warranted to explore the molecular mechanisms of this strategy.

Intra-articular injection of N-acetylglucosamine and hyaluronic acid combined with PLGA scaffolds for osteochondral repair in rabbits.

Repairing damaged articular cartilage is particularly challenging because of the limited ability of cartilage to perform self-repair. Intra-articular injections of N-acetylglucosamine (GlcNAc) comprise a method of repairing full-thickness articular cartilage defects in the rabbit knee joint model. To date, the effects of administration of GlcNAc and hyaluronic acid (HA) have been investigated only in the context of osteoarthritis treatment. Therefore, we evaluated the therapeutic effects of using cell-free porous poly lactic-co-glycolic acid (PLGA) graft implants and intra-articular injections of GlcNAc or HA in a rabbit model of osteochondral regeneration to investigate whether they have the potential for inducing osteochondral regeneration when used alone or simultaneously. Twenty-four rabbits were randomized into one of four groups: the scaffold-only group (PLGA), the scaffold with intra-articular injections of GlcNAc (PLGA+G) group, twice per week for four weeks; the scaffold with intra-articular injections of HA group (PLGA+HA) group, once per week for three weeks; and the scaffold with intra-articular injections of GlcNAc and HA (PLGA+G+HA) group, once per week for three weeks. Knees were evaluated at 4 and 12 weeks after surgery. At the end of testing, only the PLGA+G+HA group exhibited significant bone reconstruction, chondrocyte clustering, and good interactions with adjacent surfaces at 4 weeks. Additionally, the PLGA+G+HA group demonstrated essentially original hyaline cartilage structures that appeared to have sound chondrocyte orientation, considerable glycosaminoglycan levels, and reconstruction of the bone structure at 12 weeks. Moreover, the PLGA+G+HA group showed organized osteochondral integration and significantly higher bone volume per tissue volume and trabecular thickness. However, there were no significant differences between the PLGA+G and PLGA+HA groups except for gap formation on subchondral bone in the PLGA+G group. This study demonstrated that PLGA implantation combined with intra-articular injections of GlcNAc and HA allowed for cartilage and bone regeneration and significantly promoted osteochondral regeneration in rabbits without supplementation of exogenous growth factors. And the combination of this two supplements with PLGA scaffold could also prolong injection interval and better performance than either of them alone for the reconstruction of osteochondral tissue in the knee joints of rabbits.

First-in-Human Pilot Study of Implantation of a Scaffold-Free Tissue-Engineered Construct Generated From Autologous Synovial Mesenchymal Stem Cells for Repair of Knee Chondral Lesions

Background: Articular cartilage has limited healing capacity, owing in part to poor vascularity and innervation. Once injured, it cannot be repaired, typically leading to high risk for developing osteoarthritis. Thus, cell-based and/or tissue-engineered approaches have been investigated; however, no approach has yet achieved safety and regenerative repair capacity via a simple implantation procedure. Purpose: To assess the safety and efficacy of using a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stem cells (MSCs) for effective cartilage repair. Study Design: Case series; Level of evidence, 4. Methods: Five patients with symptomatic knee chondral lesions (1.5-3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove were included. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed up to 24 months postoperatively. The primary outcome was the safety of the procedure. Secondary outcomes were self-assessed clinical scores, arthroscopy, tissue biopsy, and magnetic resonance image–based estimation of morphologic and compositional quality of the repair tissue. Results: No adverse events were recorded, and self-assessed clinical scores for pain, symptoms, activities of daily living, sports activity, and quality of life were significantly improved at 24 months after surgery. Secure defect filling was confirmed by second-look arthroscopy and magnetic resonance imaging in all cases. Histology of biopsy specimens indicated repair tissue approaching the composition and structure of hyaline cartilage. Conclusion: Autologous scaffold-free TEC derived from synovial MSCs may be used for regenerative cartilage repair via a sutureless and simple implantation procedure. Registration: 000008266 (UMIN Clinical Trials Registry number).

Improving cartilage phenotype from differentiated pericytes in tunable peptide hydrogels

Differentiation of stem cells to chondrocytes in vitro usually results in a heterogeneous phenotype. This is evident in the often detected over expression of type X collagen which, in hyaline cartilage structure is not characteristic of the mid-zone but of the deep-zone ossifying tissue. Methods to better match cartilage developed in vitro to characteristic in vivo features are therefore highly desirable in regenerative medicine. This study compares phenotype characteristics between pericytes, obtained from human adipose tissue, differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the more widely used chemical induced method for chondrogenesis. Significantly higher levels of type II collagen were noted when pericytes undergo chondrogenesis in the hydrogel in the absence of induction media. There is also a balanced expression of collagen relative to aggrecan production, a feature which was biased toward collagen production when cells were cultured with induction media. Lastly, metabolic profiles of each system show considerable overlap between both differentiation methods but subtle differences which potentially give rise to their resultant phenotype can be ascertained. The study highlights how material and chemical alterations in the cellular microenvironment have wide ranging effects on resultant tissue type.

Microfluidic Encapsulation of Human Mesenchymal Stem Cells for Articular Cartilage Tissue Regeneration.

Stem cell injections for the treatment of articular cartilage damage are a promising approach to achieve tissue regeneration. However, this method is encumbered by high cell apoptosis rates, low retention in the cartilage lesion, and inefficient chondrogenesis. Here, we have used a facile, very low cost-based microfluidic technique to create visible light-cured microgels composed of gelatin norbornene (GelNB) and a poly(ethylene glycol) (PEG) cross-linker. In addition, we have demonstrated that the process enables the rapid in situ microencapsulation of human bone marrow-derived mesenchymal stem cells (hBMSCs) under biocompatible microfluidic-processing conditions for long-term maintenance. The hBMSCs exhibited an unusually high degree of chondrogenesis in the GelNB microgels with chondro-inductive media, specifically toward the hyaline cartilage structure, with significant upregulation in type II collagen expression compared to the bulk hydrogel and "gold standard" pellet culture. Overall, we have demonstrated that these protein-based microgels can be engineered as promising therapeutic candidates for articular cartilage regeneration, with additional potential to be used in a variety of other applications in regenerative medicine.

MORPHOGENESIS OF KNEE HYALINE CARTILAGE DURING INTRAARTICULAR INJECTION OF PLATELET-RICH AUTOLOGOUS PLASMA AND/OR HYALURONIC ACID PREPARATION IN RATS WITH EXPERIMENTAL OSTEOARTHRITIS

According to current concepts, the influence of autologous platelet-rich plasma (PRP) and high molecular hyaluronates (HA) on the repair of hyaline cartilage during its inflammatory and degenerative changes has been insufficiently studied yet. The objective of the work was to evaluate the morphological changes in the structure of hyaline cartilage in experimental osteoarthritis after intra-articular injection of PRP and/or HA. Material and methods. The authors used 50 adult rats of Wistar line, weighing 250±2,2 g., distributed into five groups of 10 animals (two control and three experimental groups). An experimental gonarthosis was simulated on four groups of animals. Animals of the first experimental group received intra-articular injection of PRP, the second group – HA, the third – both PRP and HA. Results. No morphological signs of degenerative and inflammatory changes in the first control group were identified. Following osteoarthritis simulation the articular cartilage thinned to 121±20,4 microns (p0,05) and the volume fraction of chondrocyte decreased to 1,2±0,6% (p0,05). The authors observed an uneven coloration of collagen fibers with severe tinctorial properties disorder of the articular cartilage matrix. After the RPR introduction the authors observed tickening of the articular cartilage up to 275±18,9 micron (p0,05) and the volume fraction of chondrocytes up to 18,4±2,0% (p0,05). The contour of the cartilage surface became smoother with the formation of a cell-free zone. Collagen fibers demonstrated a uniform distribution, tinctorial properties of cartilage matrix in all areas were preserved, no signs of inflammation were noted. After HA introduction the authors observed thickening of the cartilage plate up to 264±21,3 microns (p0,05) and the volume fraction of chondrocytes up to 11,6±1,2% (p0,05). The surface of the cartilage featured uneven contours due to multiple areas of pulping. Uneven tinctorial properties of cartilage matrix, thickness and orientation of collagen fibres were retained. No signes of inflammation were observed. After the combined consecutive application of PRP and HA cartilage thickness increased up to 268±15,3 microns (p0,05) and the volume fraction of chondrocytes increased up to 12,7±0,9% (p0,05). Individual portions of pulping on the cartilage surface were observed. Tinctorial properties of the cartilage matrix were preserved; the focal uneven staining of collagen fibers in the basal zone was observed. No signs of inflammation were noted. Conclusion. During osteoarthritis simulation in knee joints of experimental Wistar line rats the authors observed severe structural changes in articular hyaline cartilage including complete destruction accompanied by vascular proliferation and granulomatous inflammation. Intraarticular injections of PRP, HA as well as PRP in combination with HA during the simulation of osteoarthrosis were accompanied by a decrease in the severity of degenerative and dystrophic processes and improval of tinctorial properties of articular cartilage matrix. Sole application of PRP or consecutive application of PRP followed by HA were observed as having the more significant reparative effect on articular cartilage as compared to HA.

The Chondral Tissue and PRP. Theory to Support the Use

The hyaline cartilage structure is very complex, with few cells, and without blood and lymphatic vessels or nerves. This makes the healing potential very limited. Knee cartilage injuries are very common, and its treatment is a major challenge. Surgical options available nowadays like chondroplasty, microfractures, mosaicplasty and autologous chondrocyte transplantation still doesn't have satisfactory results, mainly in long term. Platelet-Rich Plasma (PRP) has been used in orthopedics since the 90's in order to stimulate tissue healing, because of its potential to concentrate platelet derived growth factors in the target place. The goal of the PRP application is to stimulate a better healing environment. PRP has been used in cartilage to treat osteoarthritis and to support treatment techniques for chondral injuries. However, the literature is still doubtful regarding the surgical results with PRP application.

Multi-Layered Scaffold to Mimic Hyaline Articular Cartilage Architecture

Articular cartilage degeneration and traumatic cartilage defects are common disorders causing pain and disability. Many strategies were developed throughout years to address these problems. Tissue engineering approaches offer several promising solutions. Articular hyaline cartilage has very complex structure and follows a multi-layer architecture. In this study, we developed a 4-layers scaffold mimicking the fibers orientation observed within the cartilage extra-cellular matrix (ECM). Bone and cartilage microparticles were incorporated in the first and second layers, respectively, to direct the differentiation of stem cells toward subchondral bone and cartilage phenotype. The 2 upper layers were designed with random (layer 3) and aligned (layer 4) electrospun nanofibers in an attempt to mimic hyaline articular cartilage ECM orientation. Histological analysis of the scaffold showed a continuous and homogeneous structure. Moreover, we confirmed the presence of cartilage and bone microparticles in the gelatin foam-based layers (layer 1 and 2). Scanning electron microscope (SEM) confirmed the tubular, vertical, morphology of the first and second layers, thereby mimicking as intended the native hyaline cartilage structure. Water uptake and degradation rate of our scaffold appeared suitable for our application, with many options for tunability. Finally, we demonstrated that the scaffolds were biocompatible, as it promoted the survival and attachment of MIAMI cells in vitro. In this study, we described the first phases of the development of a multi-layered scaffold designed to mimic the native architecture of articular hyaline cartilage. With further refinements and testing, we hope that this strategy will pave the way for potential new advances in the field of osteochondral repair. Keywords: Electrospinning, gelatin, human tissues, hyaline cartilage, MIAMI cells, multi-layered scaffold, nanofibers, tissue engineering.

EVALUATION OF THE ROLE OF ALFLUTOP IN THE OSTEOARTHRITIS TREATMENT: INDICATIONS, CLINICAL EFFICACY, TOLERABILITY AND IMPACT ON QUALITY OF LIFE

The main clinical manifestations of osteoarthritis (OA) are a painful articular syndrome of varying intensity accompanied by loss of functionality and impaired quality of life. The pathogenetic links of the degradation are related to violations of the hyaline cartilage structure. Collagen defects are practically not restored, worsening the dysfunction of joints. Alflutop is the cartilage protector, including chondroitin sulfate. In the literature its symptom - and the structure-modifying effect is shown. In the study we conducted in 60 patients the dynamics of painful articular syndrome, functional features and the quality of life of patients in case of complex treatment with alflutop were studied.

3D Bioprinting of Cartilage for Orthopedic Surgeons: Reading between the Lines.

Chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression toward osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a “layer-by-layer” deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here, we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration.

Relapsing polychondritis : A rare differential diagnosis in clinical practice

Relapsing polychondritis (RPC) is a chronic immune-mediated inflammatory, systemic disease primarily leading to structural damage and impaired function of cartilage tissue. However, the systemic inflammatory process in RPC can also affect sensory organ structures, the respiratory tract, the nervous and cardiovascular systems as well as the kidneys. The immune-mediated disease leads to recurrent inflammatory attacks causing a progressive degradation of elastic and hyaline cartilage structures, especially in the ears, nose, larynx, trachea and diarthrodial joints. However, other connective tissue structures in the eye and the heart valves may also be involved. The RPC is regarded as an orphan disease as the number of reported cases has so far remained confined to approximately 600 worldwide. The rarity of the disease has limited systematic clinical studies and the available empirical data are exclusively derived from casuistic studies or evaluation of small case series. The therapeutic interventions depend on the extent and localization of the disease manifestation. Thus, nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids and immunosuppressive agents with conventional synthetic disease-modifying antirheumatic drugs (DMARD) have been demonstrated to be beneficial. More severe and refractory diseases may require a targeted pharmacological intervention with biologic DMARDs.

Age-related Changes in the Articular Cartilage of the Stifle Joint in Non-working and Working German Shepherd Dogs

The aims of this study were to define age-related histological changes in the articular cartilage of the stifle joint in non-chondrodystrophic dogs and to determine whether physical activity has a positive impact on preservation of cartilage structure during ageing. Twenty-eight German shepherd dogs were included in the study. These dogs had no evidence of joint inflammation as defined by clinical assessment, radiology and synovial fluid analysis (specifically absence of synovial fluid serum amyloid A). The dogs were grouped as young working (n ¼ 4), young non-working (n ¼ 5), aged working (n ¼ 13) and aged non-working (n ¼ 6) animals. Gross changes in the stifle joints were recorded and biopsy samples of femoral and tibial articular cartilage were evaluated for thickness; chondrocyte number, density, surface area and morphology; isogenous group morphology; tidemark integrity; subchondral bone structure; presence of proteoglycans/ glycosaminoglycans; and expression of type I, II and X collagens. The major age-related changes, not related to type of physical activity, included elevated chondrocyte density and thinning of tibial cartilage and increased chondrocyte surface area in the superficial and intermediate zone of the femoral cartilage. There was also expression of type X collagen in the femoral and tibial calcified and non-calcified cartilage; however, type X collagen was not detected in the superficial zone of old working dogs. Therefore, ageing, with or without physical activity, leads to slight cartilage degeneration, while physical activity modulates the synthesis of type X collagen in the superficial cartilage zone, partially preserving the structure of hyaline cartilage.

A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage

The effects of Glucosamine Sulphate (GS) and Chondroitin Sulphate (CS) on the healing of damaged and repaired articular cartilage were investigated. This study was conducted using 18 New Zealand white rabbits as experimental models. Focal cartilage defects, surgically created in the medial femoral condyle, were either treated by means of autologous chondrocyte implantation (ACI) or left untreated as controls. Rabbits were then divided into groups which received either GS+/-CS or no pharmacotherapy. Three rabbits from each group were sacrificed at 12 and 24 weeks post-surgery. Knees dissected from rabbits were then evaluated using gross quantification of repair tissue, glycosaminoglycan (GAG) assays, immunoassays and histological assessments. It was observed that, in contrast to untreated sites, surfaces of the ACI-repaired sites appeared smooth and continuous with the surrounding native cartilage. Histological examination demonstrated a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. The improved regeneration of these repair sites was also noted to be significant over time (6 months vs. 3 months) and in GS and GS+CS groups compared to the untreated (without pharmacotherapy) group. Combination of ACI and pharmacotherapy (with glucosamine sulphate alone/ or with chondroitin sulphate) may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects.