Preservation Of Cartilage Research Articles

Recurrence risk of early-stage melanoma of the external ear: an investigation of surgical approach and sentinel lymph node status.

Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence. In this retrospective review of primary clinical stage 1/2 external ear melanoma, demographics, tumor characteristics, surgical resection technique (including cartilage-sparing vs. cartilage removal), and SLNB results were evaluated for recurrence risk. One hundred and fifty-six patients total had an average follow-up of 5.6 years. Twenty-nine (18.6%) patients underwent cartilage-sparing surgery and 99 (63.5%) patients underwent SLNB, 14.1% of whom had micrometastatic disease. Ten (6.4%) patients recurred loco-regionally. Recurrence was associated with Breslow depth, initial stage at diagnosis, and SLNB status. Cartilage-sparing surgery was not associated with increased recurrence. Sentinel lymph node identification rate was 100% based on clinical detection with use of lymphoscintigraphy. In addition to confirming established risk factors for melanoma recurrence, we confirm the feasibility of SLNB in stratifying recurrence risk. Although we did not see an increased recurrence risk with surgical technique and cartilage-sparing approaches, these findings are limited by small sample size.

Defining the Minimal Clinically Important Difference and Patient Acceptable Symptom State for Microfracture of the Knee: A Psychometric Analysis at Short-term Follow-up

Background: Several studies have investigated failure rates and magnitude of improvement in patient-reported outcome measures after microfracture surgery for focal chondral defects of the knee; however; what constitutes clinically significant improvement in this patient population is poorly understood. Purpose: To (1) establish the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) thresholds for microfracture surgery including the time-dependent nature of these thresholds and (2) identify predictors of achieving the MCID and PASS in patients specifically undergoing microfracture of the knee. Study Design: Case series; Level of evidence, 4. Methods: A secure institutional cartilage preservation repository was queried for all patients who underwent microfracture between 2004 and 2017. The distribution method was used to calculate MCID thresholds for the International Knee Documentation Committee (IKDC) score and the Knee injury and Osteoarthritis Outcome Score (KOOS), whereas an anchor-based method was used for the PASS. Multivariate logistic regressions were constructed to determine predictors of achieving the MCID and PASS. Results: A total of 206 patients with a mean ± SD age of 33.7 ± 13.2 years and body mass index of 26.9 ± 5.3 kg/m2 were included. All thresholds for the MCID and PASS increased over time except for the MCID thresholds for the KOOS Sports and Symptoms subscales. The proportion of patients who achieved the MCID (6 months, 78.4%; 12 months, 83.9%; 24 months, 88.6%) and PASS (6 months, 67.7%; 12 months, 79.2%; 24 months, 76.1%) generally increased over time. Older age and larger lesion size were negative independent predictors of MCID achievement. Older age was also a negative predictor of the PASS, whereas male sex and higher preoperative KOOS Symptoms and Pain scores were positive independent predictors of the PASS. Conclusion: The MCID and PASS thresholds for the IKDC and KOOS in patients undergoing microfracture of the knee are dynamic, with an increasing number of patients achieving the MCID over time. The percentage achieving the PASS increased between 6 and 12 months and then declined slightly at 24 months. Independent predictors of achieving the MCID were lesion size and age at surgery, whereas predictors of achieving the PASS included lesion size, male sex, and greater preoperative KOOS Symptoms and Pain scores.

Combined Anterior Cruciate Ligament Reconstruction and High Tibial Osteotomy in Anterior Cruciate Ligament-Deficient Varus Knees

Background: The presence of varus deformity in anterior cruciate ligament (ACL)-deficient knees can be a source of persistent knee pain owing to medial compartment overload. This deformity may threaten the outcome of ACL reconstruction because of increased tension on the graft. Methods: In the period between May 2018 to september 2019, short term pilot study including 10 patients with ACL deficiency and genu varus were treated by anatomical single bundle ACL reconstruction and open medial wedge high tibial osteotomy in same sitting. The selected patients had manifestations of ACL deficiency in association with medial joint line pain with or without lateral thrust. Prospective evaluation using the international knee documentation committee (IKDC) score was performed. The mean follow-up period was 6 months. Results: This technique achieved knee stability and realignment to normal values. The IKDC score significantly improved from 37 preoperative to 78 postoperative (p < 0.05). Conclusion: The combined procedure of ACL reconstruction and high tibial osteotomy restored knee stability and reduced pain over the medial compartment. Although the combined procedure has a longer period of rehabilitation than an isolated ACL reconstruction, the elimination of lateral thrust and preservation of articular cartilage of the medial compartment are of paramount importance to the future of these knees.

Failure of Surgery for Osteochondral Injuries of the Elbow in the Pediatric and Adolescent Population.

With an increase in single-sport specialization, elbow injuries have become increasingly common in the pediatric and adolescent population. Osteochondritis dissecans (OCD) of the capitellum frequently requires intervention yet can be difficult to treat given high patient activity demands. The purpose of this paper is to review treatment options, understand failure rates, and provide strategies for successful revision surgery. Patients at high risk for the development of this condition are involved in high-demand upper extremity activity such as baseball or gymnastics. Treatment options include non-operative management, drilling, fixation, loose body removal/microfracture, osteochondral autograft, and osteochondral allograft. Cartilage preservation procedures (i.e., osteochondral autograft) have a significant advantage in terms of clinical and radiographic healing compared with fixation or microfracture. Capitellar OCD lesions afflict a large number of adolescent athletes today and will likely continue increasing in number from sports-related injuries. It is critical to recognize and treat these lesions in a timely and appropriate fashion to optimize clinical outcomes. When faced with failure of healing, surgeons must critically analyze reasons for failure including post-operative compliance, return to high-demand sporting activity, fixation of non-viable fragments, utilization of microfracture, alignment, and concomitant pathology.

Defining Failure After Cartilage Preservation Surgery: Are We Expecting Too Much?

ABSTRACT As cartilage restoration procedures continue to be more widely performed, an associated increase in the number of patients who “fail” is inevitable. While the goal of preventing progression towards arthroplasty remains elusive, cartilage repair can delay the need for arthroplasty and improve pain and function in young and active patients, thus, at a minimum, serving as a bridging procedure. Although cartilage preservation procedures are perceived to result in high rates of failure, when examined in the context of other common orthopedic procedures such as total knee arthroplasty and anterior cruciate ligament reconstruction, the rates of unsatisfactory outcomes are relatively similar. Furthermore, despite criticism of high rates of failure after cartilage repair surgery, how this failure is defined remains rather ambiguous. Current definitions of failure often do not incorporate patient-specific outcome trajectories, and rarely consider clinically significant improvements relative to each patient's baseline level of function and goals. The purpose of the current review is to present both an objective understanding of how failure is currently defined and widely understood in the realm of cartilage repair surgery, as well as a discussion of the goals of cartilage repair, and potential definitions of success and failure of cartilage repair.

Focal Chondral and Subchondral Bone Lesions of the Knee: Current Evidence for the Use of Biologic Treatment

Abstract Focal chondral and subchondral injuries of the knee are increasingly recognized and treated pathologies. Many operative approaches to these injuries have been established, including both reparative and reconstructive procedures. More recently, biologic approaches such as platelet rich plasma, bone marrow aspirate concentrate, and stem cells have been studied as potential adjuncts following joint preserving procedures. However, outcomes of biologic injections are mixed and evolving, which may partially be due to the underappreciated role of the subchondral bone in regulating the physiologic response of cartilage to stresses. The current review provides a comprehensive synopsis of the current literature with regards to the use of intra-articular biologics following cartilage preservation surgery as well as the use of biologics in treating subchondral and bone marrow lesions.

Bioresponsive microspheres for on-demand delivery of anti-inflammatory cytokines for articular cartilage repair.

Despite innovations in surgical interventions, treatment of cartilage injury in osteoarthritic joints remains a challenge due to concomitant inflammation. Obstructing a single dominant inflammatory cytokine has shown remarkable clinical benefits in rheumatoid arthritis, and similar strategies are being suggested to target inflammatory pathways in osteoarthritis (OA). Here, we describe the utility of gelatin microspheres that are responsive to proteolytic enzymes typically expressed in arthritic flares, resulting in on-demand and spatiotemporally controlled release of anti-inflammatory cytokines for cartilage preservation and repair. These microspheres were designed with a net negative charge to sequester cationic anti-inflammatory cytokines, and the magnitude of the negative charge potential increased with an increase in crosslinking density. Collagenase-mediated degradation of the microspheres was dependent on the concentration of the enzyme. Release of anti-inflammatory cytokines from the loaded microspheres directly correlated with the degradation of the gelatin matrix. Exposure of the IL-4 and IL-13 loaded microspheres reduced the inflammation of chondrocytes up to 80%. Hence, the delivery of these microspheres in an OA joint can attenuate the stimulation of chondrocytes and the resulting secretion of catabolic factors such as proteinases and nitric oxide. The microsphere format also allows for minimally invasive delivery and is less susceptible to mechanically induced drug release. Consequently, bioresponsive microspheres can be an effective tool for cartilage preservation and arthritis treatment.

Bipolar Fresh Osteochondral Allograft Transplantation and Joint Reconstruction for Patellar and Trochlear Cartilage Defects

Patellar instability is a debilitating condition, and trauma due to the dislocations may severely damage the articular cartilage of the patellofemoral joint. The lack of healing capacity of cartilage makes treatment of such lesions challenging. In young patients, preservation of native bone and cartilage is a priority, and therefore arthroplasty procedures should be avoided even in relatively larger lesions. Fresh osteochondral allografting has been described for these difficult and complex cases, with recent studies showing promising results. In this surgical technique, we describe the use of bipolar osteochondral allografts of the patella and trochlea and patellofemoral joint reconstruction for large bipolar full-thickness cartilage defects due to recurrent dislocation events.

Rolling-sliding load decreases the loss of chondrocyte viability and the mechanical properties of cartilage explants preserved in vitro.

The viability of cartilage explants preserved in vitro decreases with time, which limits its use for transplantation. The effect of mechanical stimulation to cartilage explants in vitro is unknown. In this study, we observed the effects of mechanical stimulation on chondrocyte viability and the mechanical properties of cartilage explants preserved in vitro using a rolling-sliding loading device designed by us, and the optimal stimulation protocol was established. A cylindrical osteochondral mass drilled on the femoral condyle of a healthy pig was divided into two groups (loading group and control group), and changes in the chondrocyte survival rate, matrix composition and cartilage biomechanical properties was observed at different time points. Additionally, the mRNA expression of the apoptosis-related proteins caspase-3/Bax/Bcl-2, the cytoskeletal proteins actin/vimentin, and the matrix-related protein MMP13 were detected. The loading group exhibited delayed collagen and aggrecan degeneration and improved chondrocyte viability for three days. Protein and mRNA detection showed that apoptotic factors such as caspase-3 and Bax decreased rapidly in cartilage tissue after loading. The cytoskeletal proteins actin and vimentin showed no significant changes in mRNA expression in the control group, but was significantly higher in the loading group. MMP-13 mRNA expression was significantly higher in both the control group and loading group. Overall, this study suggests that suitable mechanical stimulation decreases the loss of chondrocyte viability and the mechanical properties of cartilage explants in vitro and improves cartilage preservation.

A placebo-controlled study comparing the efficacy of intra-articular injections of hyaluronic acid and a novel hyaluronic acid-platelet-rich plasma conjugate in a canine model of osteoarthritis

BackgroundThe objective of this study was to assess the efficacy of intra-articular injections of hyaluronic acid (HA) and a novel, on-site conjugate of HA with autologous fibrinogen in platelet-rich plasma (HA-PRP) in a canine model of osteoarthritis (OA)MethodsTwelve beagle dogs underwent a unilateral resection of the cranial cruciate ligament (CrCL) of the stifle joint. Clinical and radiographic signs of OA were confirmed in all dogs 8 weeks following CrCL resection and prior to treatment. The dogs were randomized into three groups: saline (n = 4), HA (n = 4), and HA-PRP (n = 4). Each dog received intra-articular injections of the respective substance into the affected joint at pre-determined time points. The dogs were assessed for adverse effects for 3 days after each injection and for lameness, pain, range of motion, kinetics, and radiographic OA severity prior to treatment and 3 months after injection. OA severity as determined by radiographic examination was not significantly different among the groups at any time point. The dogs were then humanely euthanatized and the stifle joint assessed by gross and histological examinations.ResultsDogs treated with four weekly injections of HA or two biweekly injections of HA-PRP were significantly (p < 0.05) better than dogs treated with four weekly injections of saline at 2-, 4-, and 12-week time points based on a comfortable range of motion (CROM) and clinical lameness score. Gait analysis measuring symmetry and weight distribution on pressure sensor walkway showed significantly (p < 0.05) improved limb function for dogs treated with HA and HA-PRP compared with dogs treated with saline yet with better clinical outcome for the HA-PRP-treated group at 12 and 20 weeks follow-up. Gross and histological analysis of synovium and articular cartilage demonstrated significant (p < 0.05) improvement by both treatments groups compared to controls. There was however significantly (p < 0.05) less damage to the cartilage in the HA-PRP group compared to the HA-treated group.ConclusionsThese data suggest that while injection of HA and HA-PRP may be sufficient for short-term amelioration of the symptoms associated with OA, treatment with HA-PRP conjugates may be superior, providing significantly better long-term cartilage preservation.

Role of Alpha-2-Microglobulin in the Treatment of Osteoarthritic Knee Pain: a Brief Review of the Literature.

Chronic knee pain remains a debilitating condition that remains difficult to manage. The purpose of this review, therefore, is to summarize current understanding of alpha-2-microglobulin in the treatment of osteoarthritic knee pain. Furthermore, we investigate its role in the anti-inflammatory properties of platelet-rich plasma (PRP). Alpha-2-microglobulin, a 720-kD protein complex, is an active protease inhibitor with tremendous anti-inflammatory properties in animal models. A growing body of evidence suggests that this complex is the most instrumental factor for cartilage preservation in PRP injections. As an active component of platelet-rich plasma's anti-inflammatory properties, alpha-2-microglobulin has been shown to be an active inhibitor of joint degeneration, cartilage preservation, and improvement in quality of life for patients with knee osteoarthritis compared with a multitude of other modalities.

Arthroscopic Medial Meniscal Transplant Using Multiple Fixation Techniques

The critical role of the meniscus in the biomechanics of the knee and articular cartilage preservation has led to an increased awareness of the importance of the meniscus. Meniscal allograft transplantation is a challenging surgical intervention that is saved as a last resort for patients who meet stringent criteria for salvage from meniscal deficiency. Proper arthroscopic implantation of a meniscal allograft takes precision and implementation of multiple fixation techniques to obtain a successful outcome.

Modeling the addition/removal of dimethyl sulfoxide into/from articular cartilage treated with the liquidus-tracking method

The successful preservation of articular cartilage (AC) is of great clinical and scientific significance. The vitreous cryopreservation of AC through the liquidus-tracking (LT) method has achieved satisfactory levels of post-warming chondrocyte survival, but the design of the entire procedure could be improved further. Mathematical modeling would help to better understand the nature and features of the LT process as experienced by the AC sample, possibly providing additional instructive data useful for guiding experimental design. In this paper, the addition/removal of the cryoprotectant dimethyl sulfoxide (Me2SO) into/from the LT-treated AC was modeled and studied numerically. The cryoprotectant permeation model and the cell membrane transport model were combined, and the spatiotemporal concentrations of Me2SO in the AC matrix and the chondrocytes were profiled. In addition, the possible injuries to the cell were predicted based on the biophysical properties of chondrocytes under both the stepwise and the continuous LT protocols. Based on these results, improvements to the stepwise LT method were proposed. Compared to the existing protocol, these improvements might eliminate two processing steps and reduce the protocol duration by 35%. Decreasing the number of processing steps and protocol duration not only saves labor and material resources, but also lowers the risk that chondrocytes will incur toxicity- and chilling-associated injury.

Effects of Rolling-Sliding Mechanical Stimulation on Cartilage Preserved In Vitro.

Mechanical stimulation is important for maintaining cartilage function. We used a loading device to exert rolling-sliding mechanical stimulation on cartilage preserved in vitro to investigate cartilage viability and the involved mechanisms. Osteochondral grafts from pig knees were randomly classified into loading and control groups. The loading group cartilage was subjected to cycles of mechanical stimulation with specified frequency/time/pressure combinations every 3days; Then the DMEM was refreshed, and the cartilage was preserved in vitro. The control group cartilage was preserved in DMEM throughout the process and was changed every 3 days. On days 14 and 28, the chondrocyte survival rate, histology, and Young's modulus of the cartilage were measured. Western blots were performed after 2h of loading to evaluate the protein expression. The loading group showed a significantly higher chondrocyte survival rate, proteoglycan and type II collagen content, and Young's modulus than did the control group on day 14, but no statistically significant differences were found on day 28. After two hours of the loading, the phosphorylation levels of MEK and ERK1/2 increased, and the expression of caspase-3, cleaved caspase-3 and bax decreased. These results suggest that periodic rolling-sliding mechanical stimulation can increase cartilage vitality in 2 weeks; a possible mechanism is that mechanical stimulation activates the MEK/ERK signalling pathway, thus inhibiting apoptotic protein expression. This loading preservation scheme could be used by cartilage tissue banks to improve cartilage preservation in vitro and enhance the quality of cartilage repair.

Defective WNT signaling may protect from articular cartilage deterioration – a quantitative MRI study on subjects with a heterozygous WNT1 mutation

WNT signaling is of key importance in chondrogenesis and defective WNT signaling may contribute to the pathogenesis of osteoarthritis and other cartilage diseases. Biochemical composition of articular cartilage in patients with aberrant WNT signaling has not been studied. Our objective was to assess the knee articular cartilage in WNT1 mutation-positive individuals using a 3.0T MRI unit to measure cartilage thickness, relaxation times, and texture features. Cohort comprised mutation-positive (N=13; age 17-76 years) and mutation-negative (N=13; 16-77 years) subjects from two Finnish families with autosomal dominant WNT1 osteoporosis due to a heterozygous missense mutation c.652T>G (p.C218G) in WNT1. All subjects were imaged with a 3.0T MRI unit and assessed for cartilage thickness, T2 and T1ρ relaxation times, and T2 texture features contrast, dissimilarity and homogeneity of T2 relaxation time maps in six regions of interest (ROIs) in the tibiofemoral cartilage. All three texture features showed opposing trends with age between the groups in the medial tibiofemoral cartilage (P=0.020-0.085 for the difference of the regression coefficients), the mutation-positive individuals showing signs of cartilage preservation. No significant differences were observed in the lateral tibiofemoral cartilage. Cartilage thickness and means of T2 relaxation time did not differ between groups. Means of T1ρ relaxation time were significantly different in one ROI but the regression analysis displayed no differences. Our results show less age-related cartilage deterioration in the WNT1 mutation-positive than the mutation-negative subjects. This suggests, that the WNT1 mutation may alter cartilage turnover and even have a potential cartilage-preserving effect.

Preservation of Autogenous Septal Cartilage for Revision Surgery.

The aim of this study is to find the ideal solution and the optimum temperature to protect the viability of the cartilage graft. This randomized prospective study consists of 30 patients with septal deviation. All patients had septoplasty operation for chronic nasal obstruction. Ten strips of cartilages were prepared from each excised septum and then immersed in formalin, alcohol (96%), saline (0,9%), gentamicin (80 mg), and cefazolin sodium (Cezol 1gr) solutions in a total of 300 vials. Those vials were stored for 6 months at both +4°C and -18°C temperatures. Two groups were compared with each other. 22 cases were male (73%) and 8 patients were female (7%). The age range was between 20 and 48 (average 25.34 ± 4.09 years). Parameters at +4°C; the cartilage volume was not significantly different among the solutions (P >0.05). Necrosis was significantly lower in the alcohol (46.7%) compared to other solutions (P = 0.001). Calcification was lower in the gentamicin group (56.7%). The loss of metachromasia was lower in the alcohol solutions (P = 0.000). Parameters at -18°C; the loss of metachromasia was higher in the gentamicin group (56.7%) than the other solutions (P = 0.003). The authors observed no significance in the rates of necrosis, calcification, metaplasia, inflammation, vascularity, or fibrosis among the solutions (P >0.05). Less necrosis and metachromosis loss in the alcohol solution indicated that alcohol was more suitable for preservation of the cartilage. In addition, temperature degree for the preservation of the cartilage did not show any significant differences.

Meniscus Subluxation Retensioning: “Autotransplant”

Knee osteoarthritis (OA) is a common condition in the older population and is characterized by several articular dysfunctions with consequent anatomic abnormalities including osteochondral degenerative changes and meniscal extrusion. Meniscal damage with extrusion is one of the strongest identified risk factors for the development and progression of knee OA and represents an important factor in the long-term health of the joint. Meniscal extrusion can alter normal knee biomechanics and dramatically inhibit meniscal function. We present a surgical technique for the treatment of early knee OA in association with an extruded meniscus to restore the meniscal anatomic position and preserve its native physiological function related to cartilage preservation. Meniscal retensioning, or a “meniscal autotransplant,” can increase meniscal coverage in the compromised compartment, prevent cartilage degeneration, decrease subchondral bone exposure, and restore the compartmental space and, consequently, can relieve patients' symptoms related to early OA.

Kartogenin hydrolysis product 4-aminobiphenyl distributes to cartilage and mediates cartilage regeneration.

Rationale The small molecule Kartogenin (KGN) promotes cartilage regeneration in osteoarthritis (OA) by activating stem cells differentiation, but its pharmacological mode-of-action remains unclear. KGN can be cleaved into 4-aminobiphenyl (4-ABP) and phthalic acid (PA) following enzymolysis of an amide bond. Therefore, this study investigated whether 4-ABP or PA exerted the same action as KGN.Methods KGN, 4-ABP and PA were analyzed in cartilage of mice after oral, intravenous or intra-articular administration of KGN by liquid chromatography-mass spectrometry method. Their effect on proliferation and chondrogenic differentiation of mesenchymal stem cells (MSC) was evaluated in vitro. Furthermore, their effect on cartilage preservation was tested in mice OA model induced by destabilization of medial meniscus. OA severity was quantified using OARSI histological scoring. Transcriptional analysis was used to find the possible targets of the chemicals, which were further validated.Results We demonstrated that while oral or intra-articular KGN delivery effectively ameliorated OA phenotypes in mice, only 4-ABP was detectable in cartilage. 4-ABP could induce chondrogenic differentiation and proliferation of MSC in vitro and promote cartilage repair in OA mouse models mainly by increasing the number of CD44+/CD105+ stem-cell and prevention of matrix loss. These effect of 4-ABP was stronger than that of KGN. Transcriptional profiling of 4-ABP-stimulated MSC suggested that RPS6KA2 and the PI3K-Akt pathway were 4-ABP targets; 4-ABP could activate the PI3K-Akt pathway to promote MSC proliferation and repair OA injury, which was blocked in RPS6KA2-knockdown MSC or RPS6KA2-deficient mice.Conclusion 4-ABP bio-distribution in cartilage promotes proliferation and chondrogenic differentiation of MSC, and repairs osteoarthritic lesions via PI3K-Akt pathway activation.

Preservation of Knee Articular Cartilage.

Hyaline articular cartilage is critical for the normal functioning of the knee joint. Untreated focal cartilage defects have the potential to rapidly progress to diffuse osteoarthritis. Over the last several decades, a variety of interventions aiming at preserving articular cartilage and preventing osteoarthritis have been investigated. Reparative cartilage procedures, such as microfracture, penetrate the subchondral bone plate in effort to fill focal cartilage defects with marrow elements and stimulate fibrocartilaginous repair. In contrast, restorative cartilage procedures aim to replace the defective articular surface with autologous or allogeneic hyaline cartilage. This review focuses on the preservation of articular cartilage, and discusses the current reparative and restorative surgical techniques available for treating focal cartilage defects.

IL6 receptor blockade preserves articular cartilage and increases bone volume following ischemic osteonecrosis in immature mice

Juvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL6) is predominantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL6. This study investigated whether an inhibition of IL6 receptor improves cartilage preservation and bone healing in JIO. A small animal model (i.e., 6-week-old mouse) of JIO was treated with either saline or tocilizumab, an IL6 receptor blocker, for 6 weeks. TUNEL-positive chondrocytes in the articular cartilage were reduced by the tocilizumab treatment, concomitant with the increase in cartilage matrix. The levels of a cartilage anabolic marker Sox9 was significantly increased in the articular cartilage of mice treated with tocilizumab. Micro-CT assessment showed tocilizumab treatment significantly increased trabecular epiphyseal bone volume (P=0.001, n=10), thickness (P=0.007) and number (P=0.014) and decreased bone separation (P=0.002) and its deformity (P=0.003). A bone formation marker, BMP2, and an angiogenic marker, vascular endothelial growth factor (VEGF), were both significantly increased by tocilizumab treatment under hypoxia using human chondrocytes while the bone resorption marker, RANKL/OPG ratio, was reduced. Tocilizumab treatment following ischemic osteonecrosis has cartilage anabolic effect and increases bone volume in JIO mouse model. The findings lead to a possible application of tocilizumab for preclinical study using a large animal model of JIO and a clinical trial to validate this treatment.