Blood-induced Cartilage Damage Research Articles

Blood-induced cartilage damage alters the ankle joint load during walking.

Ankle cartilage damage due to repeated joint bleeds often leads to altered gait in adult patients with hemophilia. It is therefore of clinical importance to develop an understanding of the biomechanical gait features in hemophilia patients with and without blood-induced cartilage damage and age-matched control subjects. We recruited a control group (n = 17), patients with hemophilia (PwH) without blood-induced ankle cartilage damage (PwH_NoCartDam , n = 5) and PwH with severe blood-induced ankle cartilage damage (PwH_CartDam , n = 19). We collected three-dimensional gait analysis data with following outcome variables in the ankle, Chopart and the first metatarsophalangeal (MTP 1) joints: range of motion (ROM) during stance phase, peak joint moment and powers. Biomechanical loading (BW) was quantified as the joint reaction forces using inverse dynamic analysis. Loading rate (BW/s) and impulse (BW*s) were calculated between 50% and 70% of stance phase. All biomechanical variables of the ankle joint were significantly lowered in the PwH_CartDam group compared with both the control subjects and the PwH_NoCartDam group. No compensatory biomechanical function was observed in other foot joints. An ankle loading rate of 2.64 ± 0.83 BW/s was observed in the control group, which was significantly higher than 1.75 ± 0.43 BW/s (P = .049) and 1.22 ± 0.59 BW/s (P < .001) in respectively the PwH_NoCartDam group and PwH_CartDam group. Patients with severe blood-induced cartilage damage demonstrated a (mal)adaptive gait strategy as they experience difficulties to properly unload the ankle cartilage during walking.

Proteoglycan synthesis rate as a novel method to measure blood-induced cartilage degeneration in non-haemophilic and haemophilic rats.

IntroductionHaemophilic animal models are used to study blood‐induced cartilage damage, but quantitative and sensitive outcome measures are needed.AimTo develop a novel quantitative method for detecting early cartilage degeneration in a haemophilic rat model of blood‐induced joint damage.MethodsThe 35Sulphate incorporation (35SO4 2− assay) was applied to tibial and patellar cartilage of wild‐type rats to quantify baseline proteoglycan synthesis and to evaluate the effect of 4‐day blood exposure in vitro. Next, haemarthrosis was induced in 39 FVIII‐deficient rats and characterized by changes in knee joint diameter and development of bone pathology (using micro‐CT). Four‐ and 16‐day posthaemarthrosis proteoglycan synthesis rate (PSR) was assessed using the 35SO4 2− assay, with the contralateral knee as control.ResultsIn vitro, a decrease in PSR in tibial and patellar cartilage was demonstrated following blood exposure. In vivo, joint diameter and development of bone pathology confirmed successful induction of haemarthrosis. In the blood‐exposed knee, tibial and patellar PSR was inhibited 4 and 16 days after induced haemarthrosis. Interestingly, at day 16 the proteoglycan synthesis in the contralateral knee was also inhibited to an extent correlating with that of the blood‐exposed knee.ConclusionFor the first time, early changes in cartilage matrix synthesis upon blood exposure were quantified with the 35SO4 2− assay in a haemophilic rat model, establishing this assay as a novel method to study blood‐induced cartilage damage.

A fusion protein of interleukin‐4 and interleukin‐10 protects against blood‐induced cartilage damage in vitro and in vivo

Background Joint damage still causes significant morbidity in hemophilia. It results from synovial inflammation and direct cartilage-degenerating properties of blood components. Interleukin (IL)-4 and IL-10 have been shown to protect cartilage from blood-induced damage. Recently an IL4-10 fusion protein has been developed to combine the function of IL-4 and IL-10 and increase their bioavailability. Objectives In this study we evaluate whether this IL4-10 fusion protein protects against blood-induced joint damage. Methods In vitro, human cartilage explants were exposed to whole blood and simultaneously to a broad concentration range of the IL4-10 fusion protein. Effects on cartilage matrix turnover were compared with the individual cytokines. Moreover, the influence of the fusion protein and its individual components on IL-1β and IL-6 production was investigated. In hemophilia A mice, the effect of intra-articular treatment on synovitis and cartilage damage resulting from joint bleeding was evaluated by histochemistry. Results In vitro, the fusion protein prevented blood-induced cartilage damage in a dose-dependent manner, with equal effectiveness to the combination of the separate cytokines. In whole blood cultures 10 ng mL-1 fusion protein completely blocked the production of IL-1β and IL-6 by monocytes/macrophages. In hemophilic mice, intra-articular injection of IL-4 and IL-10 did not influence synovitis or cartilage degeneration. In contrast, equimolar amounts of the fusion protein attenuated cartilage damage upon repeated joint bleeding, although synovial inflammation was hardly affected. Conclusions Overall, this study shows that the IL4-10 fusion protein prevents blood-induced cartilage damage in vitro and ameliorates cartilage degeneration upon joint bleeding in hemophilic mice.

Why Synergism between Researches and Orthopaedics is still not Enough? Role of IL-1 Beta in Blood Induced Cartilage Damage

Why Synergism between Researches and Orthopaedics is still not Enough? Role of IL-1 Beta in Blood Induced Cartilage Damage

A fusion protein of interleukin-4 and interleukin-10 protects against blood-induced cartilage damage in vitro and in vivo

A fusion protein of interleukin-4 and interleukin-10 protects against blood-induced cartilage damage in vitro and in vivo

IL-1β, in contrast to TNFα, is pivotal in blood-induced cartilage damage and is a potential target for therapy

AbstractJoint bleeding after (sports) trauma, after major joint surgery, or as seen in hemophilia in general leads to arthropathy. Joint degeneration is considered to result from the direct effects of blood components on cartilage and indirectly from synovial inflammation. Blood-provided proinflammatory cytokines trigger chondrocytes and induce the production of cartilage-degrading proteases. In the presence of erythrocyte-derived iron, cytokines stimulate radical formation in the vicinity of chondrocytes inducing apoptosis. To unravel the role of interleukin (IL) 1β and tumor necrosis factor (TNF) α in the pathogenesis of this blood-induced cartilage damage, the effect of antagonizing these cytokines was examined in human in vitro cultures. Addition of recombinant human IL-1β monoclonal antibody or IL-1 receptor antagonist resulted in a dose- and time-dependent protection of cartilage from blood-induced damage. In higher concentrations, almost complete normalization of cartilage matrix proteoglycan turnover was achieved. This was accompanied by a reduction in IL-1β and IL-6 production in whole blood cultures, whereas TNFα production remained unaffected. Interestingly, addition of a TNFα monoclonal antibody, although demonstrated to inhibit the direct (transient) effects of TNFα on cartilage, exhibited no effect on blood-induced (prolonged) cartilage damage. It is demonstrated that IL-1β is crucial in the development of blood-induced joint damage, whereas TNFα is not. This hierarchical position of IL-1β in blood-induced joint damage warrants studies on targeting IL-1β to potentially prevent joint degeneration after a joint bleed.

Interleukin-1beta is essential for blood-induced cartilage damage in vitro

Interleukin-1beta is essential for blood-induced cartilage damage in vitro

Interleukin-1β Is Essential for Blood-Induced Cartilage Damage In Vitro

Objective: Joint damage due to recurrent joint bleeds remains the most common complication in hemophilia. The combination of cartilage degeneration and synovial inflammation ultimately lead to hemophilic arthropathy. Cartilage destruction is considered to result from both cartilage matrix-degrading proteases as well as cartilage-destructive pro-inflammatory cytokines such as interleukin (IL)-1b. To unravel the role of IL1b in the pathogenesis of blood-induced cartilage damage, we investigated whether direct blocking of IL1b specifically prevents blood-induced cartilage damage in vitro. Moreover, we investigated whether blocking IL1b after the onset of a bleed can still avert cartilage damage.Methods: Full thickness healthy human articular cartilage explants, obtained post-mortem, were cultured for four days in presence or absence of 50% v/v whole blood. A recombinant human IL1b monoclonal antibody (IL1bmAb) was added at the moment of blood exposure in a concentration of 0, 1, 3, 10, 30, or 100ng/mL (n=8). Furthermore, 100ng/mL IL1bmAb was administered directly or after a delay of several hours up to two days (n=7). Cartilage matrix proteoglycan turnover was determined 12 days later to analyse long-term effects.To investigate the direct effects of IL1bmAb on cartilage, explants were cultured for four days in the presence of 10ng/mL IL1bmAb in the absence of blood (n=7).Results: Exposure to blood decreased the proteoglycan synthesis rate and -content, and increased the proteoglycan release (all p<0.05). Adding IL1bmAb resulted in a dose-dependent increase of the proteoglycan synthesis rate leading to normalisation at higher concentrations (see figure A). Proteoglycan release and -content also normalised after addition of IL1bmAb. Its protective effect was most pronounced when IL1bmAb was administered within 4 hours after the bleed, but significant recovery was still achieved by administration within 8-24 hours (see figure B for proteoglycan synthesis). In the absence of blood, IL1bmAb did not have direct effects on cartilage proteoglycan turnover (for all three parameters p>0.50).Conclusions: This study demonstrates that IL1b is a crucial factor in the development of blood-induced cartilage damage in vitro. Blocking this pro-inflammatory cytokine with a monoclonal antibody protects cartilage from the damaging effects of blood exposure in a dose-dependent way. Early administration after blood-exposure is most beneficial. Further research is warranted to investigate the in vivo capacity of IL1bmAb in prevention and its position as a treatment to limit joint damage upon joint bleeding. [Display omitted] Figure -Effect ofIL1bmAbon cartilage proteoglycan synthesis rate is dose-dependent (A) and time-dependent (B). Median values ± IQR of at least 7 individual cartilage and blood donors are shown. Hash tags indicate a statistically significant difference from control values, whereas asterisks indicate a statistically significant difference from blood-exposed cartilage withoutIL1bmAb addition(p<0.05). DisclosuresSchutgens:CSL Behring: Research Funding.

Long non-coding rnas in osteoarthritis and chondrogenesis

Long non-coding rnas in osteoarthritis and chondrogenesis

Interleukin-1B IS essential for blood-induced cartilage damage in vitro

Purpose: Exposure of joint cartilage to blood can occur after joint trauma, during or after major joint surgery, or due to hemophilia. This ultimately leads to joint damage, both by direct effects of blood on cartilage and via synovial inflammation. Cartilage destruction is considered to result from both cartilage matrix-degrading proteases as well as cartilage-destructive pro-inflammatory cytokines such as IL1β. To unravel the role of IL1β in the pathogenesis of blood-induced cartilage damage, we investigated whether direct blocking of IL1β specifically prevents blood-induced cartilage damage in vitro. Methods: Full thickness healthy human articular cartilage explants, obtained post-mortem, were cultured for 4 days in presence or absence of 50% v/v whole blood. A recombinant human IL1β monoclonal antibody (IL1β mAb) was only added during blood exposure in a concentration of 0, 1, 2, 10, 30, or 100 ng/mL. Cartilage matrix proteoglycan turnover was determined 12 days later to analyse long-term effects. Moreover, to investigate the direct effects of IL1β mAb on cartilage, explants were cultured for 4 days in the presence of 10 ng/mL IL1β mAb in the absence of blood. Results: Exposure to blood decreased the proteoglycan-synthesis rate (-62%) and proteoglycan content (-19%), and increased the proteoglycan release (+191%, all p < 0.05). Adding IL1βmAb resulted in a dose-dependent increase of the proteoglycan synthesis rate leading to normalisation at higher concentrations (see figure A). Moreover, proteoglycan release was statistically significantly decreased from a concentration of 3ng/mL and above (see figure B). Similar, the proteoglycan content increased statistically significantly upon addition of the IL1βmAb (3 ng/mL and above; all p < 0.05). In the absence of blood, IL1βmAb did not have direct effects on cartilage proteoglycan turnover (p = 0.51). Conclusions: This study demonstrates that IL1β is a crucial factor in the development of blood-induced cartilage damage in vitro. Blocking this pro-inflammatory cytokine with a monoclonal antibody protects cartilage from the damaging effects of blood exposure. Further research is warranted to investigate the in vivo capacity of IL1β mAb in prevention and its position as a treatment of hemophilic arthropathy.

A fusion protein of IL4 and IL10 (IL4-10 synerkine), is very effective in protecting cartilage from blood-induced damage

Purpose: Interleukin 4 (IL4), IL10 or the combination of both protects cartilage from blood-induced damage in vitro. Because IL4 and IL10 use different signaling pathways they are able to exert different, but also potentially additive effects. It has been postulated that they can act in synergy enhancing their beneficial effects and controlling their individual adverse effects. Therefore a combination of IL4 and IL10 might be the best option to administer in vivo. To overcome the low bioavailability of IL4 and IL10 in vivo, a fusion protein has been developed: IL4-10 synerkine. It has been demonstrated that this novel drug inhibits numerous pro-inflammatory cytokines secreted by monocytes and T-cells. This study investigates whether this IL4-10 synerkine protects against blood-induced cartilage damage similarly as the combination of the individual components. Methods: Human cartilage explants were exposed to 50% v/v whole blood for 4 days and simultaneously to a broad concentration range (0-100 ng/mL) of the IL4-10 synerkine. Effects of 10 ng/mL IL4-10 synerkine were compared to the same concentrations of the individual cytokines and the combination. Cartilage matrix proteoglycan turnover was assessed after a recovery period of 12 days. Moreover, the influence of IL4-10 synerkine (10 ng/mL) and its individual components on levels of IL1β and IL6 were investigated in a 4 days 50% v/v whole blood culture. Results: Exposure to 50% v/v whole blood resulted in a clear statistical significant decrease of proteoglycan (PG) synthesis rate (-74%; p = 0.012) and an increase of PG release (+92%, p = 0.017) compared to control. Adding of IL4-10 synerkine, resulted in a clear dose-response curve, leading to full normalisation of PG synthesis rate and -release at higher concentrations (>10 ng/mL). These results were similar to the effect of the two individual cytokines combined (see figure). The individual cytokines had a more distinct profile where IL4 was superior over IL10 (see figure). Moreover, addition of IL4-10 synerkine reduced IL1β and IL6 production in whole blood cultures to control levels (both p < 0.05), similar to the combination of IL4 plus IL10 (p = 0.180 and p = 0.173, respectively). Conclusions: IL4-10 synerkine strongly protects against blood-induced cartilage damage in vitro, presumably at least in part by reduction of pro-inflammatory cytokines including IL1β and IL6. Considering better bioavailability and more easy application of this synerkine compared to the individual cytokines, testing the IL4-10 synerkine in an in vivo model of blood-induced cartilage damage is warranted.

Deferasirox limits cartilage damage following haemarthrosis in haemophilic mice.

Joint bleeds in haemophilia result in iron-mediated synovitis and cartilage damage. It was evaluated whether deferasirox, an iron chelator, was able to limit the development of haemophilic synovitis and cartilage damage. Haemophilic mice were randomly assigned to oral treatment with deferasirox (30 mg/kg) or its vehicle (control) (30 mg/kg). Eight weeks after start of treatment, haemarthrosis was induced. After another five weeks of treatment, blood-induced synovitis and cartilage damage were determined. Treatment with deferasirox resulted in a statistically significant (p< 0.01) decrease in plasma ferritin levels as compared to the control group (823 ng/ml ± 56 and 1220 ng/ml ±114, respectively). Signs of haemophilic synovitis, as assessed by the Valentino score [range 0 (normal) - 10 (most affected)], were not different (p=0.52) when comparing the control group with the deferasirox group. However, deferasirox treatment resulted in a statistically significant (p< 0.01) reduction in cartilage damage, as assessed by the loss in Safranin O staining [range 0 (normal) - 6 (most affected)], when comparing the deferasirox group with the control group: score 2 (65.4 % vs 4.2 %), score 3 (26.9 % vs 4.2 %), score 4 (7.7 % vs 20.8 %), score 5 (0 % vs 54.2 %), and score 6 (0 % vs 16.7 %). Treatment with deferasirox limits cartilage damage following the induction of a haemarthrosis in haemophilic mice. This study demonstrates the role of iron in blood-induced cartilage damage. Moreover, these data indicate that iron chelation may be a potential prevention option to limit the development of haemophilic arthropathy.

A short time window to profit from protection of blood-induced cartilage damage by IL-4 plus IL-10

IL-4 plus IL-10 prevents blood-induced cartilage damage. The aim of the present study was to evaluate whether cartilage damage can still be averted by addition of IL-4 plus IL-10 when added after the onset of a bleed and whether aspiration of blood prior to addition of IL-4 plus IL-10 is of additive protective value. Healthy canine hip and human shoulder cartilage was exposed to whole blood for 4 days. IL-4 plus IL-10 was administered directly or after a delay of several hours up to 2 days. Furthermore, blood was aspirated after 1 or 2 days and subsequently IL-4 plus IL-10 was added. IL-1β concentration and cartilage matrix proteoglycan turnover were determined. Exposure of canine and human cartilage to blood decreased the proteoglycan synthesis rate and content and increased proteoglycan release. IL-4 plus IL-10 only prevented blood-induced damage of canine cartilage when added directly, not after 4 h or later. For human cartilage, IL-4 plus IL-10 limited blood-induced damage as well as IL-1β production when administered within 4-8 h after the onset of a bleed, but not thereafter. Aspiration of blood within 24 h fully prevented cartilage damage. Subsequent addition of IL-4 plus IL-10 was not of additive value. For humans, there is a short time window after onset of a joint bleed in which IL-4 plus IL-10 can limit blood-induced cartilage damage. Furthermore, aspiration of a joint to shorten blood exposure fully prevents cartilage damage. Both options can be considered in the treatment of a joint haemorrhage.

A single intra‐articular injection with IL‐4 plus IL‐10 ameliorates blood‐induced cartilage degeneration in haemophilic mice

The combination of interleukin (IL)-4 and IL-10 protects against blood-induced cartilage damage in vitro. It has been hypothesized that the combination of these cytokines is effective if applied early in the process of cartilage damage. The present study investigated whether a single intra-articular injection of IL-4 plus IL-10 immediately after a joint bleed limits cartilage damage in an in vivo haemophilia mouse model of blood-induced joint damage. Factor VIII knockout mice with severe haemophilia A were punctured once with a needle below the patella to induce a joint haemorrhage. Subsequently IL-4 plus IL-10 (n = 24) or vehicle (n = 24) was injected intra-articularly. After 35 days, the time needed for development of detectable joint degeneration, knee joints were examined for cartilage damage by macroscopic and microscopic evaluation. A single intra-articular injection of IL-4 plus IL-10 ameliorated progression of cartilage degeneration caused by a single joint bleed to a certain extent. No effect on inflammation was observed at this time point. A single intra-articular injection of IL-4 plus Il-10 directly after a single joint bleed limits progression of cartilage degeneration over time. Improved bioavailability (half-life) of both cytokines might improve their protective ability in the development of cartilage degeneration, and probably also inflammation.

IL-4 alone and in combination with IL-10 protects against blood-induced cartilage damage

It has been reported that interleukin (IL)-10 limits blood-induced cartilage damage. Our aim was to study the effect of IL-4 alone and in combination with IL-10 on blood-induced cartilage damage. Healthy human full thickness cartilage explants were cultured for 4 days in the presence of 50% v/v blood. IL-4, IL-10, or a combination of both cytokines was added during blood exposure. Cartilage matrix turnover was determined after a recovery period; additionally cytokine production, chondrocyte apoptosis, and expression of the IL-4 and IL-10 receptors were analyzed directly after exposure. Blood-induced damage to the cartilage matrix was limited by IL-4 in a dose-dependent way (P<0.05). Also IL-10 limited this damage, although to a lesser extent (P<0.03). The effect of IL-4 plus IL-10 was more pronounced and protective than IL-10 alone (P<0.05). Production of IL-1β and tumor necrosis factor (TNF)-α was limited by both IL-4 and IL-10 (P<0.05), but more strongly by IL-4. Blood-induced apoptosis of chondrocytes was limited by IL-4 and the combination, and not by IL-10 alone. No direct beneficial effect of IL-4 or IL-10 on cartilage was found, however, the chondrocyte receptor expression of both cytokine receptors was upregulated by exposure to blood. This study demonstrates that IL-4 alone and in combination with IL-10 prevents blood-induced cartilage damage. Expectedly, anti-inflammatory effects on monocytes in the blood fraction and protective effects on chondrocytes are both involved. IL-4 in combination with IL-10 might be used to prevent blood-induced joint damage as a result of trauma or surgery.

220 BRADYKININ, THROUGH B 2 RECEPTORS, ACTIVATES THE RELEASE OF THE CYTOKINE INTERLEUKIN 6, THE CHEMOKINE INTERLEUKIN 8, AND THE METALLOPROTEINASE 3 IN HUMAN KNEE CHONDROCYTES

Results: Cartilage cultured in the presence of blood showed a decrease of proteoglycan synthesis rate of 70%, an increase of proteoglycan release of 100%, and a decrease of proteoglycan content of 15% after 16 days of culture (all p<0.05). This blood-induced damage of the cartilage matrix was limited by IL-4 in a clear dose-dependent way. Addition of 100 ng/ml IL-4 during blood-exposure reduced the proteoglycan synthesis rate with only 45%, and decreased the proteoglycan release with 30% compared to control (all p<0.05). Moreover, proteoglycan content was normalized. The combination of IL-4 and IL-10 was clearly more protective against damage caused by blood. This was especially evident for the proteoglycan synthesis which was completely normalized. Furthermore, treatment with a combination of the two cytokines was significantly better than the effect of IL-4 and IL-10 alone (p<0.05). Conclusions: Besides IL-10, as shown previously, also IL-4 protects against blood-induced cartilage damage. The combination of these two cytokines is clearly the most protective. In addition to the direct effects on cartilage, both cytokines are synergistic in inhibition of inflammation. As such, this justifies further evaluation of the combination of IL-4 and IL-10 in prevention and treatment of blood-induced joint damage.

Histopathological modifications in haemophilic synovial tissue

Haemophilia is characterised by spontaneous bleeding, mainly in the larger joints. Repeated bleeding episodes lead to synovitis and then to haemophilic arthropathy (HA) with synovial changes, cartilage damage and bone...

Interleukin-10 and Articular Cartilage: Experimental Therapeutical Approaches in Cartilage Disorders

Interleukin (IL)-10 is a well known anti-inflammatory and immunoregulatory cytokine, mainly released by, and acting on cells of the immune system such as monocytes, macrophages, T cells, NK cells, and B cells. IL-10 is also produced by a few connective tissue cell types including chondrocytes and is involved in processes such as connective tissue extracellular matrix remodelling, although it's exact function in articular cartilage remains unclear. This review article summarizes after a short insight into functions of IL-10 in the immune system most of the published literature on the role of IL-10 in articular cartilage homeostasis and disorders. A critical analysis of the present literature was undertaken leading to a survey of the significance of IL-10 in rheumatoid arthritis (RA), osteoarthritis (OA) and blood induced cartilage damage with particular focus on the direct impact of IL-10 on chondrocyte biology. IL-10 is up-regulated in RA and OA and therapeutic effects of IL-10 in experimental arthritis using several gene therapeutic approaches were reported, mainly through an immune cell mediated immunosuppression mechanism. Recently, a direct anti-inflammatory, -catabolic and -apoptotic potential of IL-10 in cartilage was described, suggesting a chondroprotective effect of IL-10, not only in RA and OA, but also in non-RA and non-systemic cartilage disorders. Chondroprotection by IL-10 may be a promising tool in arthritis therapy, as IL-10 plays a role in joint and cartilage immunoregulation and homeostasis. However, a crucial problem remains to be the optimisation of local and continuous therapeutic effective levels of IL-10 administration in the joint.

Heat-shock proteins and their role in chondrocyte protection, an application for autologous transplantation

Articular cartilage injury presents a unique therapeutic challenge. As cartilage possesses no blood or nerve supply of its own it has a particular susceptibility to early injury and a poor capacity for self-repair. Treatment options are limited and injury can eventually lead to osteoarthritis. Autologous chondrocyte transplantation is an exciting therapeutic development, but despite initial encouraging results, graft failure and formation of fibro- as opposed to hyaline cartilage remain problematic. Bleeding is an inevitable consequence of surgery, and blood-induced cartilage damage is well documented. It is hypothesised here that protecting chondrocytes against blood could significantly improve results. Heat-shock protein induction may confer chondroprotection. The expression of heat-shock proteins in human chondrocytes and rat femoral head cartilage following heat shock was analysed by Western blotting, and red-blood-cell-induced chondrocyte death was assessed by cell viability and apoptosis by flow cytometry. We demonstrate that heat-shock induced expression of heat-shock protein 70 (HSP70) (rat and human) and HSP32 (human). Blood and blood products reduced rat cartilage proteoglycan synthesis and human chondrocyte viability, and induced human chondrocyte apoptosis at concentrations considerably lower than those reported previously. The induction of HSP70 in rat cartilage was ineffective in reducing chondrocyte death in the absence or presence of red blood cells or red cell products. Heat shock to human chondrocytes reduced low levels of apoptosis (<20%) and cell death induced by low levels of blood products, but not higher levels. Induction of HSP32 with diacetylrhein appeared to be more effective and may hold greater promise. Blood has potent adverse effects on chondrocytes and the induction and chondroprotective effects of heat-shock proteins could be applied to increase the initial success of implanted chondrocytes improving the outcome of autologous chondrocyte transplantation.

Assessment of Blood-Induced Cartilage Damage in Rabbit Knees Using Scanning Electron Microscopy

To investigate the harmful effects of a single episode of intra-articular bleeding on articular cartilage of rabbit knees using scanning electron microscopy. Autologous blood was injected into the right knee joints of 18 New Zealand white rabbits. Surface and cellular damages were examined by the scanning electron microscope (n=9) and light microscope (n=34), respectively. The injected right knees were then compared with the corresponding control left knees at one, 3, and 6 weeks after the blood injection. The articular surface of the injected knees turned uniformly rough with multiple pits after one week. Maximal changes with elevations and depressions were observed at 3 weeks. These changes reversed at 6 weeks with the irregularities smoothing out. A similar pattern of transient cartilage damage was noted histologically. Both scanning electron microscopic and light microscopic findings suggest that a single episode of intra-articular bleeding leads to articular cartilage damage but this appears to be reversible. Our findings of transient damage to the articular cartilage suggest that there is no need for intra-articular evacuation and washout following an acute episode of haemarthrosis.