Degenerative Cartilage Changes Research Articles

Research Progress on the Application of Icariin in Osteoarthritis Treatment

Osteoarthritis (OA) is a multifaceted bone and joint disease with degenerative changes of articular cartilage. Therefore, the current research on the etiology of OA mainly focuses on the etiology of articular cartilage degeneration. Clarifying the pathogenesis of OA from the molecular level has become an important research topic in the field of orthopedics. Its main pathological features are the decrease of chondrocyte metabolic activity, cartilage matrix degradation, and osteophyte formation. Icariin (ICA) is the main active monomer of epimedium, a traditional Chinese medicine, and the pharmacological research has revealed favorable effects of ICA on the bone system. ICA can promote the proliferation of chondrocytes and inhibit the apoptosis of chondrocytes, alleviate the degradation rate of cartilage matrix, and effectively protect articular cartilage. This review also expounds the mechanism of promoting cartilage repair.

Do partial glenohumeral degenerative changes in patients undergoing arthroscopic rotator cuff repair influence clinical outcomes?

BackgroundThe prognostic factors for patients with full-thickness rotator cuff tears (RCTs) include tear size, muscle atrophy and fatty infiltration. However, the influence of early coexisting degenerative changes on RCT outcomes is unappreciated. The purpose of this study was to calculate the impact that pre-existing partial glenohumeral cartilaginous changes have on patients undergoing arthroscopic RCT repair.MethodsA study of 54 patients undergoing arthroscopic RCT repair was undertaken. The presence of co-existing patches of glenohumeral degenerative cartilaginous changes and RCT size was recorded at surgery. Pre- and postoperative outcomes were assessed using traditional (Oxford Shoulder Score [OSS], 5-level EuroQol-5D [EQ-5D-5L] questionnaire and EuroQol visual analog scale [EQ-VAS]) and patient-centric re-formatted prisms. Outcomes were assessed as an entire dataset, and sub-group analysis was performed according to the grade of co-existing arthritis and tear size.ResultsSignificant improvements (p<0.05) in clinical outcomes were recognized when assessed using either the traditional or reformatted prisms (average % improvements in OSS, EQ-5D-5L and EQ-VAS were 47%, 33% and 43%, respectively; average improvements in pain, function, and psychological well-being were 48%, 33% and, 29%, respectively). Positive gain was noted in all sub-groups of arthritic grading and tear size.ConclusionsGood clinical outcomes can be achieved following RCT repair even in the presence of local partial degenerative cartilage changes and advancing tear size. These benefits are patient-centered but require RCT repairability.

Effect of cold on knee osteoarthritis: Recent research status

Abstract Osteoarthritis is a common chronic irreversible joint disease characterized by degenerative changes of articular cartilage and secondary hyper osteogeny. Knee osteoarthritis(KOA) affects not only the articular cartilage, but also the entire joint, including subchondral bone, joint capsule, synovial membrane, meniscus, ligaments, periarticular muscles, and tendons. The primary aim of treatment is to relieve symptoms, delay joint degeneration, and maximally maintain patient's quality of life. There are many risk factors contributing to the development of KOA, including climate. This review will discuss the relationship between climate in cold region and KOA and the possibility of modifying risk factors such as the environment for the prevention and treatment of KOA.

Combination of Lidocaine and IL-1Ra Is Effective at Reducing Degradation of Porcine Cartilage Explants

Background: Posttraumatic inflammation after joint injury, ranging from sprains to articular fracture, contributes to the development of arthritis, and the administration of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) is a potential intervention to mitigate this response. Although IL-1Ra mitigates cartilage degenerative changes induced by IL-1, lidocaine is used for local pain management in acute joint injury. Intra-articular delivery of both drugs in combination would be a novel and possibly disease–modifying treatment. However, it is not known whether the interaction with lidocaine at clinical concentrations (1%) would alter the efficacy of IL-1Ra to protect cartilage from the catabolic effects of IL-1. Hypothesis: Treatment of articular cartilage with IL-1Ra in combination with a clinically relevant concentration of lidocaine (1%) will inhibit the catabolic effects of IL-1α in a manner similar to treatment with IL-1Ra alone. Study Design: Controlled laboratory study. Methods: Fresh porcine cartilage explants were harvested, challenged with IL-1α, and incubated for 72 hours with IL-1Ra or a combination of IL-1Ra and lidocaine. The primary outcome was total sulfated glycosaminoglycan (sGAG) release. Additional experiments assessed the effect of storage temperature and premixing of IL-1Ra and lidocaine on sGAG release. All explants were histologically assessed for cartilage degradation using a modified Mankin grading scale. Results: The combination of IL-1Ra and lidocaine, premixed at various time points and stored at room temperature or 4°C, was as effective as IL-1Ra alone at inhibiting IL-1α–mediated sGAG release. Mankin histopathology scores supported these findings. Conclusion: Our hypothesis was supported, and results indicated that the combination of IL-1Ra and lidocaine was as efficacious as IL-1Ra treatment alone in acutely mitigating biological cartilage injury due to IL-1α in an explant model. Clinical Significance: The combination of IL-1Ra and lidocaine is stable when reagents are stored in advance of administration at varying temperatures, providing clinically relevant information about storage of medications. The ability to premix and store this drug combination for intra–articular delivery may provide a novel treatment after joint injury to provide pain relief and block inflammation–induced catabolism of joint tissues.

Dipolar Relaxation of Water Protons in the Vicinity of a Collagen-like Peptide.

Quantitative magnetic resonance imaging is one of the few available methods for noninvasive diagnosis of degenerative changes in articular cartilage. The clinical use of the imaging data is limited by the lack of a clear association between structural changes at the molecular level and the measured magnetic relaxation times. In anisotropic, collagen-containing tissues, such as articular cartilage, the orientation dependency of nuclear magnetic relaxation can obscure the content of the images. Conversely, if the molecular origin of the phenomenon would be better understood, it would provide opportunities for diagnostics as well as treatment planning of degenerative changes in these tissues. We study the magnitude and orientation dependence of the nuclear magnetic relaxation due to dipole–dipole coupling of water protons in anisotropic, collagenous structures. The water–collagen interactions are modeled with molecular dynamics simulations of a small collagen-like peptide dissolved in water. We find that in the vicinity of the collagen-like peptide, the dipolar relaxation of water hydrogen nuclei is anisotropic, which can result in orientation-dependent relaxation times if the water remains close to the peptide. However, the orientation-dependency of the relaxation is different from the commonly observed magic-angle phenomenon in articular cartilage MRI.

Change in knee cartilage components in stroke patients with genu recurvatum analysed by zero TE MR imaging

Genu recurvatum in stroke patients with hemiplegia causes readily cumulative damage and degenerative changes in the knee cartilage. It is important to detect early cartilage lesions for appropriate treatment and rehabilitation. The purpose of this cross-sectional study was to provide a theoretical basis for the early rehabilitation of hemiplegia patients. We used a zero TE double-echo imaging sequence to analyse the water content in knee joint cartilage at 12 different sites of 39 stroke patients with genu recurvatum and 9 healthy volunteers using a metric similar to the porosity index. When comparing the hemiplegic limb vs. the nonhemiplegic limb in patients, the ratios of the deep/shallow free water content of the femur cartilages at the anterior horn (1.16 vs. 1.06) and posterior horn (1.13 vs. 1.25) of the lateral meniscus were significantly different. Genu recurvatum in stroke patients with hemiplegia can cause changes in the moisture content of knee cartilage, and the changes in knee cartilage are more obvious as the genu recurvatum increases. The "healthy limb" can no longer be considered truly healthy and should be considered simultaneously with the affected limb in the development of a rehabilitation treatment plan.

Eldecalcitol regulates the gene expressions of articular cartilage markers and differentiation markers in chondrocytes

Vitamin D has been shown to reduce symptoms in patients with osteoarthritis (OA). In a previous study, local administration of eldecalcitol, an active vitamin D3 analog, reduced degenerative changes in articular cartilage in the early phase of experimental OA. However, the target of vitamin D in OA remains unknown. Here, we investigated the effect of eldecalcitol treatment on chondrocytes, which were divided into superficial zone chondrocytes (SZC), deep zone chondrocytes (DZC), and differentiated chondrocytes. SZC and DZC were cultured in monolayer and 3D pellet cultures treated with eldecalcitol. The gene expressions of articular cartilage and chondrocyte differentiation markers were evaluated. Histological analysis of SZC and DZC 3D pellet cultures was performed. The results showed that the articular cartilage markers ETS-related gene (Erg) and lubricin/proteoglycan 4 (PRG4) were significantly increased in SZC, but not in DZC, in the monolayer culture treated with eldecalcitol. The chondrocyte differentiation markers type X collagen and alkaline phosphatase (ALP) were significantly decreased in the DZC pellet culture treated with eldecalcitol. Immunochemical analysis also showed that Erg and lubricin/PRG4 expressions were elevated in the SZC pellet culture treated with eldecalcitol, while type X collagen and ALP expressions were decreased in the DZC pellet culture treated with eldecalcitol. In conclusion, this study showed that eldecalcitol upregulated articular cartilage markers in SZC and suppressed differentiation markers in DZC. Such regulation of chondrocytes by eldecalcitol could be potentially effective against OA progression.

Axial alignment is a critical regulator of knee osteoarthritis.

Although osteoarthritis (OA), a leading cause of disability, has been associated with joint malalignment, scientific translational evidence for this link is lacking. In a clinical case study, we provide evidence of osteochondral recovery upon unloading symptomatic isolated medial tibiofemoral knee OA associated with varus malalignment. By mapping response correlations at high resolution, we identify spatially complex degenerative changes in cartilage after overloading in a clinically relevant ovine model. We further report that unloading diminishes OA cartilage degeneration and alterations of critical parameters of the subchondral bone plate in a similar topographic fashion. Last, therapeutic unloading shifted the articular cartilage and subchondral bone phenotype to normal and restored several physiological correlations disturbed in neutral and varus OA, suggesting a protective effect on the integrity of the entire osteochondral unit. Collectively, these findings identify modifiable trajectories with considerable translational potential to reduce the burden of human OA.

β2-Adrenoceptor Deficiency Results in Increased Calcified Cartilage Thickness and Subchondral Bone Remodeling in Murine Experimental Osteoarthritis.

PurposeRecent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of knee OA in β2-AR-deficient (Adrb2-/- ) mice after surgical OA induction.MethodsOA was induced by destabilization of the medial meniscus (DMM) in male wildtype (WT) and Adrb2-/- mice. Cartilage degeneration and synovial inflammation were evaluated by histological scoring. Subchondral bone remodeling was analyzed using micro-CT. Osteoblast (alkaline phosphatase - ALP) and osteoclast (cathepsin K - CatK) activity were analyzed by immunostainings. To evaluate β2-AR deficiency-associated effects, body weight, sympathetic tone (splenic norepinephrine (NE) via HPLC) and serum leptin levels (ELISA) were determined. Expression of the second major AR, the α2-AR, was analyzed in joint tissues by immunostaining.ResultsWT and Adrb2-/- DMM mice developed comparable changes in cartilage degeneration and synovial inflammation. Adrb2-/- DMM mice displayed elevated calcified cartilage and subchondral bone plate thickness as well as increased epiphyseal BV/TV compared to WTs, while there were no significant differences in Sham animals. In the subchondral bone of Adrb2-/- mice, osteoblasts activity increased and osteoclast activity deceased. Adrb2-/- mice had significantly higher body weight and fat mass compared to WT mice. Serum leptin levels increased in Adrb2-/- DMM compared to WT DMM without any difference between the respective Shams. There was no difference in the development of meniscal ossicles and osteophytes or in the subarticular trabecular microstructure between Adrb2-/- and WT DMM as well as Adrb2-/- and WT Sham mice. Number of α2-AR-positive cells was lower in Adrb2-/- than in WT mice in all analyzed tissues and decreased in both Adrb2-/- and WT over time.ConclusionWe propose that the increased bone mass in Adrb2-/- DMM mice was not only due to β2-AR deficiency but to a synergistic effect of OA and elevated leptin concentrations. Taken together, β2-AR plays a major role in OA-related subchondral bone remodeling and is thus an attractive target for the exploration of novel therapeutic avenues.

Quadriceps muscle strength at 2years following anterior cruciate ligament reconstruction is associated with tibiofemoral joint cartilage volume.

Quadriceps strength deficits following anterior cruciate ligament reconstruction (ACLR) are linked to altered lower extremity biomechanics, tibiofemoral joint (TFJ) space narrowing and cartilage composition changes. It is unknown, however, if quadriceps strength is associated with cartilage volume in the early years following ACLR prior to the onset of posttraumatic osteoarthritis (OA) development. The purpose of this cross-sectional study was to examine the relationship between quadriceps muscle strength (peak and across the functional range of knee flexion) and cartilage volume at ~ 2years following ACLR and determine the influence of concomitant meniscal pathology. The involved limb of 51 ACLR participants (31 isolated ACLR; 20 combined meniscal pathology) aged 18-40years were tested at 2.4 ± 0.4years post-surgery. Isokinetic knee extension torque generated in 10° intervals between 60° and 10° knee flexion (i.e. 60°-50°, 50°-40°, 40°-30°, 30°-20°, 20°-10°) together with peak extension torque were measured. Tibial and patellar cartilage volumes were measured using magnetic resonance imaging (MRI). The relationships between peak and angle-specific knee extension torque and MRI-derived cartilage volumes were evaluated using multiple linear regression. In ACLR participants with and without meniscal pathology, higher knee extension torques at 60°-50° and 50°-40° knee flexion were negatively associated with medial tibial cartilage volume (p < 0.05). No significant associations were identified between peak concentric or angle-specific knee extension torques and patellar cartilage volume. Higher quadriceps strength at knee flexion angles of 60°-40° was associated with lower cartilage volume on the medial tibia ~ 2years following ACLR with and without concomitant meniscal injury. Regaining quadriceps strength across important functional ranges of knee flexion after ACLR may reduce the likelihood of developing early TFJ cartilage degenerative changes. III.

Comparative characteristics of changes in subchondral bone of rats after antenatal glucocorticoid administration and modeling of osteoporosis

Background. Osteoporosis is a progressive systemic bone disease that results in decreased bone mineral density and, as a result, increases the risk of bone fractures. Changes that occur in the subchondral bone in osteoporosis or because of hormones can cause degenerative changes in the articular cartilage that underlie osteoarthritis. Objective. The aim of the study was to identify and compare morphological changes that occur in the subchondral bone in experimental simulations of osteoporosis and in adult rats that were born from females that were exposed to glucocorticoid solution administration in the 3rd trimester of pregnancy. Methods. Tibias of 26 white mature laboratory rats were studied. In serial sections, the relative areas occupied by bone trabeculae and lacunae were calculated. Results. The relative area involving the bone trabeculae (23,2 ± 3,70%) statistically significantly decreased at 21 day in the group of animals that undergone a simulation of osteoporosis in comparison with the control group. Similar changes are observed in the group of experimental animals that were born from females that were exposed to glucocorticoid solution administration in the 3rd trimester of pregnancy. Conclusion. Thus, the results of the study demonstrate the similarity of morphological changes occurring in the subchondral bone in rats that undergone a simulation of osteoporosis and rats that were born from females that were exposed to glucocorticoid solution administration in the 3rd trimester of pregnancy.

Meniscus Injury and its Surgical Treatment Does not Increase Initial Whole Knee Joint Friction.

While it is generally accepted that traumatic meniscus pathologies lead to degenerative articular cartilage changes in the mid-to long-term and consecutively to post-traumatic osteoarthritis (PTOA), very little is known about how such injuries initiate tribological changes within the knee and their possible impact on PTOA acceleration. Therefore, the aim of this study was to investigate the influence of three different medial meniscus states (intact, posterior root tear, total meniscectomy) on the initial whole knee joint friction. Six ovine knee joints were tested in a passive pendulum friction testing device under an axial load of 250 N and an initial deflection of 12°, representing swing phase conditions, and under an axial load of 1000 N and an initial deflection of 5°, simulating stance phase conditions. To additionally consider the influence of the time-dependent viscoelastic nature of the knee joint soft tissues on whole joint friction, the tests were performed twice, directly following load application and after 20 min creep loading of either 250 N or 1000 N axial load. On the basis of a three-dimensional joint kinematic analysis, the energy loss during the passive joint motion was analyzed, which allowed considerations on frictional and damping processes within the joint. The so-called “whole knee joint” friction was evaluated using the boundary friction model from Stanton and a viscous friction model from Crisco et al., both analyzing the passive joint flexion-extension motion in the sagittal plane. Significantly lower friction coefficients were observed in the simulated swing phase after meniscectomy (p < 0.05) compared to the intact state. No initial whole joint friction differences between the three meniscus states (p > 0.05) were found under stance phase conditions. Soft tissue creeping significantly increased all the determined friction coefficients (p < 0.05) after resting under load for 20 min. The exponential decay function of the viscous friction model provided a better fit (R 2∼0.99) to the decaying flexion-extension data than the linear decay function of the boundary friction model (R 2∼0.60). In conclusion, this tribological in vitro study on ovine knee joints indicated that neither a simulated posterior medial meniscus root tear nor the removal of the medial meniscus resulted in an initially increased whole joint friction.

Elder Mice Exhibit More Severe Degeneration and Milder Regeneration in Temporomandibular Joints Subjected to Bilateral Anterior Crossbite.

Temporomandibular joints (TMJs) have a biomechanical relationship with dental occlusion. Aberrant occlusion initiates degenerative remodeling responses in TMJ condyles. Aging is a promoting factor of osteoarthritis (OA) development. The aim of this study was to assess the effect of aging on degenerative remodeling in TMJ condyles in response to occlusal biomechanical stimulation caused by the installation of aberrant prostheses and observe rehabilitation after their removal. The experiments involved 84 female C57BL/6J mice (42 at 6 weeks old and 42 at 28 weeks old). A bilateral anterior crossbite (BAC) model was developed, and the TMJs were sampled at 3, 7, and 11 weeks. BAC was removed at 7 weeks in a subset of mice, which accepted BAC treatment at 6 week of age, and maintained for another 4 weeks after BAC removal. TMJ changes were assessed with micro-CT, histomorphology, immunohistochemistry (IHC), and immunofluorescence staining assays. The results showed that BAC induced typical OA-like TMJ lesions that were more severe in the elder groups as evaluated by the acellular zones, clustered chondrocytes, fissures between cartilage and subchondral bone, reductions in matrix amount and the cartilage thickness as revealed by histomorphological measurements, and subchondral bone loss as detected on micro-CT images. IHC indicated significant increases in cleaved caspase-3-expressing cells and decreases in ki67-positive cells in the BAC groups. There were obvious age-dependent changes in the numbers of superficial zone cells and CD90-expressing cells. Supportively, cleaved caspase-3-expressing cells obviously increased, while ki67-expressing cells significantly decreased with aging. In the elder BAC groups, the superficial zone cells such as CD90-expressing cells were greatly reduced. At 11 weeks, the superficial zone cells were almost non-existent, and there were clear serrated injuries on the cartilage surface. BAC removal attenuated the degenerative changes in the condylar cartilage and subchondral bone. Notably, the rescue effect was more pronounced in the younger animals. Our findings demonstrate the impacts of aging on both TMJ degenerative changes in response to BAC and regenerative changes following BAC removal. The reduced number of chondro-progenitor cells in aged TMJ cartilage provides an explanation for this age-related decline in TMJ rehabilitative behaviors.

The role of diacereins in the treatment of osteoarthritis from the point of view of a new paradigm of pathogenesis

Among the most common diseases of humanity in patients of the older age group, there is an articular pathology with degenerative changes in the hyaline cartilage, which significantly limits the functional activity of the locomotor apparatus. The rapid development of experimental scientific research in recent decades has made it possible to revise the concept of the pathogenesis of this process with confirmation of the leading role of inflammation in the development of functional and structural damage in this disease. These new data supported the change in the name of the disease from “osteoarthros” to “osteoarthritis” and justified the positive effects of individual drugs. The proposed lecture material discloses the topic of the modern understanding of the pathogenesis of osteoarthritis and the additional benefits of using drugs from the diacerein group due to their anti‑inflammatory and chondroprotective effect.

Progress of Signaling Pathways, Stress Pathways and Epigenetics in the Pathogenesis of Skeletal Fluorosis

Fluorine is widely dispersed in nature and has multiple physiological functions. Although it is usually regarded as an essential trace element for humans, this view is not held universally. Moreover, chronic fluorosis, mainly characterized by skeletal fluorosis, can be induced by long-term excessive fluoride consumption. High concentrations of fluoride in the environment and drinking water are major causes, and patients with skeletal fluorosis mainly present with symptoms of osteosclerosis, osteochondrosis, osteoporosis, and degenerative changes in joint cartilage. Etiologies for skeletal fluorosis have been established, but the specific pathogenesis is inconclusive. Currently, active osteogenesis and accelerated bone turnover are considered critical processes in the progression of skeletal fluorosis. In recent years, researchers have conducted extensive studies in fields of signaling pathways (Wnt/β-catenin, Notch, PI3K/Akt/mTOR, Hedgehog, parathyroid hormone, and insulin signaling pathways), stress pathways (oxidative stress and endoplasmic reticulum stress pathways), epigenetics (DNA methylation and non-coding RNAs), and their inter-regulation involved in the pathogenesis of skeletal fluorosis. In this review, we summarised and analyzed relevant findings to provide a basis for comprehensive understandings of the pathogenesis of skeletal fluorosis and hopefully propose more effective prevention and therapeutic strategies.

Histological Study of Hyaline Articular Cartilage changes in a Rat Model of Complete Freund’s Adjuvant-Induced arthritis of the Knee Joint

Background: Arthritis is the most common joint disorder. The most significant structural change seen in arthritis is the degeneration of the articular cartilage. Numerous animal models are used to reproduce arthritis. In this paper, we assessed the ability of complete Freund's adjuvant (CFA) to induce degenerative changes of hyaline articular cartilage in rat chronic arthritis model. Methods: In this study, 42 adult male albino rats were used, divided into: control group I (18 rats) and arthritis group II (24 rats). Arthritis was induced unilaterally by a single intra-articular injection of 125 μl of CFA in the right knee joint of each rat. The samples were collected 2, 6, and 10 weeks post-injection. Hematoxylin & Eosin (H&E) stain, Masson’s trichrome stain, Safranin O (S.O) stain were used to assess articular cartilage degeneration during inflammation. Results: The articular cartilage of rats of arthritis group II showed progressive inflammatory cell infiltration in the synovial membrane. Chondrocytes showed degeneration, hypertrophy and extensive proliferation. Moreover, the matrix exhibited fibrillations, fissuring, delamination and denudation with fibrous tissue within the denuded surface. The thickness of the articular cartilage, the collagen content and the proteoglycan content showed significant decrease in rats sacrificed after 10 weeks compared to rats sacrificed after 2 weeks and 6 weeks from the onset of the experiment. Conclusions: Intra-articular injection of complete Freund’s adjuvant induces progressive degeneration of the hyaline articular cartilage of the knee joint of rats. It can be useful for studies on mechanisms and strategy of treatment of knee joint arthritis.

RAAV-Mediated sox9 Overexpression Improves the Repair of Osteochondral Defects in a Clinically Relevant Large Animal Model Over Time In Vivo and Reduces Perifocal Osteoarthritic Changes

Background: Gene transfer of the transcription factor SOX9 with clinically adapted recombinant adeno-associated virus (rAAV) vectors offers a powerful tool to durably enhance the repair process at sites of osteochondral injuries and counteract the development of perifocal osteoarthritis (OA) in the adjacent articular cartilage. Purpose: To examine the ability of an rAAV sox9 construct to improve the repair of focal osteochondral defects and oppose perifocal OA development over time in a large translational model relative to control gene transfer. Study Design: Controlled laboratory study. Methods: Standardized osteochondral defects created in the knee joints of adult sheep were treated with rAAV-FLAG-hsox9 relative to control (reporter) rAAV-lacZ gene transfer. Osteochondral repair and degenerative changes in the adjacent cartilage were monitored using macroscopic, histological, immunohistological, and biochemical evaluations after 6 months. The microarchitecture of the subchondral bone was assessed by micro–computed tomography. Results: Effective, prolonged sox9 overexpression via rAAV was significantly achieved in the defects after 6 months versus rAAV-lacZ treatment. The application of rAAV-FLAG-hsox9 improved the individual parameters of defect filling, matrix staining, cellular morphology, defect architecture, surface architecture, subchondral bone, and tidemark as well as the overall score of cartilage repair in the defects compared with rAAV-lacZ. The overexpression of sox9 led to higher levels of proteoglycan production, stronger type II collagen deposition, and reduced type I collagen immunoreactivity in the sox9- versus lacZ-treated defects, together with decreased cell densities and DNA content. rAAV-FLAG-hsox9 enhanced semiquantitative histological subchondral bone repair, while the microstructure of the incompletely restored subchondral bone in the sox9 defects was not different from that in the lacZ defects. The articular cartilage adjacent to the sox9-treated defects showed reduced histological signs of perifocal OA changes versus rAAV-lacZ. Conclusion: rAAV-mediated sox9 gene transfer enhanced osteochondral repair in sheep after 6 months and reduced perifocal OA changes. These results underline the potential of rAAV-FLAG-hsox9 as a therapeutic tool to treat cartilage defects and afford protection against OA. Clinical Relevance: The delivery of therapeutic rAAV sox9 to sites of focal injuries may offer a novel, convenient tool to enhance the repair of osteochondral defects involving both the articular cartilage and the underlying subchondral bone and provide a protective role by reducing the extent of perifocal OA.

ACL reconstruction, medial meniscus repair and high tibial osteotomy done as a single stage procedure in a case of neglected ACL and partial medial meniscus tear with a subsequent varus knee: A case report

A long standing anterior cruciate ligament (ACL) tear causes progressive degenerative changes in the knee. This leads to secondary meniscal lesions, cartilage degenerative changes and subsequent varus angulation.A 27 year old male footballer presented to us with a traumatic right knee pain and swelling with recurrent instability, since 8 years. On examination there was knee laxity with an obvious varus deformity of the right leg. Radiographs showed medical compartment osteoarthritis and MRI was suggestive of a chronic ACL and medial meniscus tear. A single step salvage procedure of ACL reconstruction, medial meniscus repair and valgus producing high tibial osteotomy (HTO) was done for this patient. Post operatively there was no knee laxity and instability. At one year follow up, the patient had a satisfactory outcome with a painless and complete knee range of motion and had full weight bearing.In this case report we have shown how a single step salvage procedures with biological reconstructions can be done for patients with chronic ACL and medial meniscus tear patients with varus angulation, with a good outcome. Hence, simultaneous reconstructions of the ACL and medial meniscus with HTO can be used as a novel management technique to delay arthroplasty in young patients with unstable arthritic knees.

Changes of the condylar cartilage and subchondral bone in the temporomandibular joints of rats under unilateral mastication and expression of Insulin-like Growth Factor-1

This study aimed to define changes in the rat condylar cartilage and subchondral bone using the unilateral mastication model. In this study, forty 4-week-old Wistar rats were randomly divided into experimental (n=20) and control group (n=20). In the experimental group, unilateral dental splints were placed on the occlusal surface of left maxillary molars. The rats were sacrificed at 1, 2, 3, and 4 weeks after placement of the splint. Micro-CT scanning and histological staining were performed to observe the changes in the mandibular condylar cartilage and subchondral bone. Levels of insulin-like growth factor-1 (IGF-1) were determined via immunohistochemistry to analyse the occurrence of osteogenic changes. Micro-CT scanning findings demonstrated the occurrence of asymmetric growth of condyle in the experimental group. The condylar cartilage and subchondral bone exhibited degradation on the chewing side of the experimental group and showed decreased bone mineral density, thinner cartilage thickness, and increased degree of degeneration and osteoclast activity. Compared with the control group, the expression of IGF-1 was remarkably higher on the non-chewing side. Long-term unilateral mastication can lead to the occurrence of degenerative changes in the condylar cartilage and subchondral bone during growth and development. IGF-1 may play a role in promoting the process of osteogenesis.

Modified poloxamer 407 and hyaluronic acid thermosensitive hydrogel-encapsulated keratinocyte growth factor 2 improves knee osteoarthritis in rats

Osteoarthritis (OA) is one of the most common chronic diseases, causing degenerative changes in articular cartilage and subchondral bones. To date, there is no effective drug to delay the progression of OA in clinical practice. In this study, we synthesized and prepared a new thermosensitive hydrogel called PHA hydrogel, a mixture of normal poloxamer 407 and hyaluronic acid-modified poloxamer 407, and we investigated the effects of the PHA hydrogel loaded with keratinocyte growth factor 2 (KGF-2) on rats with papain-induced OA. First, we evaluated the safety of the PHA hydrogel in vitro and in vivo. The results showed that the PHA hydrogel had suitable osmotic pressure and no obvious cytotoxicity or adverse reactions after intra-articular injection. In addition, the PHA hydrogel improved the stability of KGF-2. Next, we studied the effects of the PHA hydrogel loaded with KGF-2 (PHA-KGF-2) on OA in rats. PHA-KGF-2 significantly improved the morphology and inflammation of the articular cartilage, reduced the loss of proteoglycan, and balanced collagen metabolism compared with KGF-2 alone. These data demonstrated that the PHA hydrogel is a safe biomaterial that can protect KGF-2, and thus is a promising therapeutic strategy for patients with OA.