Large osteochondral defect in the lateral femoral condyle reconstructed by Atelocollagen-associated autologous chondrocyte implantation combined with anterior cruciate ligament reconstruction.

BACKGROUND: Articular surface damage commonly associated with rupture of the anterior cruciate ligament (ACL). Large osteochondral defect, which consists of a severe depression fracture and a large cartilage defect, need to be treated due to deformation of the articular surface as it can impact the clinical outcome of ACL reconstruction. Although autologous chondrocyte implantation is one of the useful options in such cases, it can be questioned whether the reconstruction of the ACL and osteochondral defect should be performed in one procedure alone. CASE PRESENTATION: We report a case of a 38-year-old male with a deep depression fracture extending to the edge of the lateral femoral condyle associated with ACL injury after twisting his right knee while skiing. The patient was successfully treated with tissue-engineered cartilage transplantation covered by the periosteum with an iliac bone graft combined with anatomic double-bundle ACL reconstruction. Histopathological examination of the transplanted cartilage taken at second-look arthroscopy showed a cartilage-like tissue in the middle to deep zone in which the extracellular matrix was largely stained with Safranin O. The patient was able to return to his previous level of skiing activity without any experience of knee pain. Magnetic resonance imaging at 4 years after surgery showed that the graft integrated to the border zone and subchondral bone. The operated knee showed negative Lachman test and had a full range of motion. CONCLUSIONS: To our knowledge, this is the first report of anatomic double-bundle ACL reconstruction with tissue-engineered cartilage transplantation and an iliac bone graft to restore the lateral edge of the femoral condyle.

Interruption of glycosphingolipid synthesis enhances osteoarthritis development in mice.

OBJECTIVE: Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions. GSL expression is decreased in the articular cartilage of humans with osteoarthritis (OA). This study was undertaken to determine the functional role of GSLs in cartilage metabolism related to OA pathogenesis in mice. METHODS: We generated mice with knockout of the chondrocyte-specific Ugcg gene, which encodes an initial enzyme of major GSL synthesis, using the Cre/loxP system (Col2-Ugcg(-/-) mice). In vivo OA and in vitro cartilage degradation models were used to evaluate the effect of GSLs on the cartilage degradation process. RESULTS: Although Col2-Ugcg(-/-) mice developed and grew normally, OA changes in these mice were dramatically enhanced with aging, through the overexpression of matrix metalloproteinase 13 and chondrocyte apoptosis, compared to their wild-type (WT) littermates. Col2-Ugcg(-/-) mice showed more severe instability-induced pathologic OA in vivo and interleukin-1α (IL-1α)-induced cartilage degradation in vitro. IL-1α stimulation of chondrocytes from WT mice significantly increased Ugcg messenger RNA expression and up-regulated GSL metabolism. CONCLUSION: Our results indicate that GSL deficiency in mouse chondrocytes enhances the development of OA. However, this deficiency does not affect the development and organization of cartilage tissue in mice at a young age. These findings indicate that GSLs maintain cartilage molecular metabolism and prevent disease progression, although GSLs are not essential for chondrogenesis of progenitor and stem cells and cartilage development in young mice. GSL metabolism in the cartilage is a potential target for developing a novel treatment for OA.

Alterations of high-mannose type N-glycosylation in human and mouse osteoarthritis cartilage.

OBJECTIVE: The process of N-glycosylation is involved in the pathogenesis of various diseases. However, little is known about the contribution of changes in N-glycans in osteoarthritis (OA). The aim of this study was to identify the alterations in N-glycans in human OA cartilage, to characterize the messenger RNA (mRNA) expression of N-glycan biosynthesis enzyme genes (N-glycogenes) in mouse articular chondrocytes during cartilage degradation, and to analyze the relationship between altered N-glycan patterns and mechanisms of cartilage degradation. METHODS: Alterations in N-glycans were analyzed in human OA cartilage and degraded mouse cartilage by high-performance liquid chromatography and mass spectrometry. N-glycogene mRNA expression in mouse chondrocytes was measured using reverse transcription-polymerase chain reaction. To assess the relationship between the altered N-glycans and degradation of mouse cartilage, experiments involving either knockdown or overexpression of N-glycogenes were performed in mouse articular chondrocytes. RESULTS: Alterations in high-mannose type N-glycans were observed in both human OA cartilage and degraded mouse cartilage. The expression of ß1,2N-acetylglucosaminyltransferase I (GlcNAc-TI) mRNA, which converts high-mannose type N-glycans, was significantly increased in degraded mouse cartilage. Mouse chondrocytes with suppressed GlcNAc-TI expression had reduced levels of matrix metalloproteinase 13 (MMP-13) and ADAMTS-5 (aggrecanase 2) mRNA following stimulation with interleukin-1α (IL-1α). In contrast, mouse chondrocytes overexpressing GlcNAc-TI had increased levels of MMP-13 and ADAMTS-5 mRNA following stimulation with IL-1α. CONCLUSION: These findings indicate that alterations in high-mannose type N-glycans and N-glycogenes in chondrocytes correlate with the release of MMP-13 and ADAMTS-5 during cartilage degradation. These findings suggest that N-glycans play a crucial role in the initiation and progression of OA.

The medial gap is a reliable indicator for intraoperative soft tissue balancing in posterior-stabilized total knee arthroplasty.

BACKGROUND: Appropriate soft tissue balance and accurate alignment are important for successful total knee arthroplasty (TKA). However, the optimal technique for establishing and measuring soft tissue balancing remains unclear. The aim of this study was to analyze the intraoperative medial and lateral gap pattern using digital knee balancer in posterior-stabilized (PS) TKA. METHODS: This study involved 55 patients with medial osteoarthritis who underwent a primary TKA using an image-free navigation system. The extension gap and the flexion gap at 90° knee flexion were assessed using an offset seesaw-type digital balancer. Continuous joint distraction force from 10 lb to 60 lb was applied. Medial gap, lateral gap, and varus angle were measured. RESULTS: The medial bone gap difference between extension and flexion was constant regardless of the distraction force from 20 lb to 60 lb. The lateral bone gap was significantly greater than the medial bone gap in extension and flexion from 30 lb to 60 lb (P < 0.05). The varus angle changed depending on the distraction force, especially in flexion. The varus angle in flexion was significantly greater than that in extension from 40 lb to 60 lb (P < 0.05). CONCLUSIONS: The medial bone gap is a reliable indicator unaffected by the distraction force during surgery and is useful for adjusting the medial gap in extension and flexion appropriately to ensure medial stability in PS-TKA. The digital knee balancer and navigation system support both precise gap assessment and surgery.

Preoperative knee deformity and kinematics impact postoperative knee kinematics in total knee arthroplasty.

BACKGROUND: The purpose of this study was to evaluate the relationship between the preoperative knee deformity/kinematic pattern and the postoperative knee kinematic pattern in posterior cruciate ligament substituting (PS)-total knee arthroplasty (TKA). METHODS: This study involved 39 patients with medial osteoarthritis who underwent a primary PS-TKA using a computed-tomography-based navigation system. All the operations were performed by a single surgeon using a subvastus approach, modified gap technique and the same PS type of prosthesis (Genesis II™ total knee system, Smith & Nephew, Memphis, TN, USA). Knee deformity, kinematic pattern after capsule incision (preoperative knee kinematics), and kinematic pattern after implantation (postoperative knee kinematics) in PS-TKA were measured. Kinematic patterns were divided into two groups: a medial pivot group and a non-medial pivot group. RESULTS: Preoperative varus knee deformity was significantly larger in the non-medial pivot group than in the medial pivot group (femorotibial angle: 184.7±6.4° vs. 180.8±3.9°, P<0.05). In addition, preoperative knee kinematics were conserved postoperatively, at a rate of 82% (P<0.01). CONCLUSIONS: The severity of varus knee deformity and the preoperative knee kinematic pattern might have affected the postoperative knee kinematics in PS-TKA. This must be confirmed with a randomized controlled trial on a large population study. LEVEL OF EVIDENCE: case control study, Level III.

Ganglioside GM3 has an essential role in the pathogenesis and progression of rheumatoid arthritis.

Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder that principally attacks synovial joints, afflicts over 2 million people in the United States. Interleukin (IL)-17 is considered to be a master cytokine in chronic, destructive arthritis. Levels of the ganglioside GM3, one of the most primitive glycosphingolipids containing a sialic acid in the structure, are remarkably decreased in the synovium of patients with RA. Based on the increased cytokine secretions observed in in vitro experiments, GM3 might have an immunologic role. Here, to clarify the association between RA and GM3, we established a collagen-induced arthritis mouse model using the null mutation of the ganglioside GM3 synthase gene. GM3 deficiency exacerbated inflammatory arthritis in the mouse model of RA. In addition, disrupting GM3 induced T cell activation in vivo and promoted overproduction of the cytokines involved in RA. In contrast, the amount of the GM3 synthase gene transcript in the synovium was higher in patients with RA than in those with osteoarthritis. These findings indicate a crucial role for GM3 in the pathogenesis and progression of RA. Control of glycosphingolipids such as GM3 might therefore provide a novel therapeutic strategy for RA.