Progression of varus deformity in osteoarthritic knees induces anterior paradoxical motion of the femur during early knee flexion.

PURPOSE: The purpose of this study was to investigate the position of the femur relative to the tibia throughout range of motion in the osteoarthritic knee to evaluate knee kinematics and assess its relationship with the degree of varus deformity. METHODS: In this study, 116 preoperative knees with varus deformity were evaluated using a navigation system. The internal-external, anteroposterior, and mediolateral positions of the femur relative to the tibia were measured at maximum extension, 15°, 30°, 45°, 60°, 90°, 105°, and 120°, and maximum flexion angles. From these parameters, two-dimensional translation of the surgical epicondylar axis was projected onto the tibial axial plane, and the femoral movement was evaluated relative to the tibia. In addition, the knees were retrospectively classified into three groups according to their degrees of preoperative hip-knee-ankle angle: mild (< 10°), moderate (10°-20°), and severe (> 20°). Then, the differences in each parameter between these groups were investigated. The Steel-Dwass test was performed to identify the difference among three groups. Statistical significance was set at p values < 0.05. RESULTS: There was a significant difference in the anteroposterior position of the femur relative to the tibia among the three groups, especially from extension to early flexion (p < 0.05). The anteroposterior position at knee extension deviated posteriorly according to the progression of varus deformity. Rotational and mediolateral translation were not significantly different among the groups. Normal knee kinematics were diminished in almost all cases in each group. In addition, anterior paradoxical motion of the femur during early knee flexion was observed in 45.6% (n = 26), 57.1% (n = 28), and 80.0% (n = 8) of cases in the mild, moderate, and severe groups, respectively. The anteroposterior position of the femur relative to the tibia at knee extension was significantly more posterior in patients with than in those without anterior paradoxical motion (p < 0.0001). CONCLUSION: The anteroposterior position of the femur relative to the tibia changed according to the progression of varus deformity in osteoarthritic knees, especially from knee extension to early flexion. Posterior deviation of the femur at knee extension induced its anteroposterior movement relative to the tibia, resulting in anterior paradoxical motion. LEVEL OF EVIDENCE: III.

Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty.

OBJECTIVES: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS. METHODS: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively. RESULTS: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups. CONCLUSIONS: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.

In vivo anterior cruciate ligament length pattern assessment secondary to differences in the femoral attachment under loading condition using image-matching techniques.

BACKGROUND: The anterior cruciate ligament is composed of two functional bundles and is crucial for knee function. There is limited understanding of the role of each individual bundle and the influence on length pattern due to difference in bone tunnel position under loading conditions throughout the range of motion. We measured point to point length between the femoral and tibial footprints of the ligament throughout the range of motion in normal knees, under normal loading conditions, and investigated length pattern changes secondary to differences in the femoral footprint. We hypothesized that anteromedial and posterolateral bundles have complementary roles, and the ligament length pattern is influenced by the footprint position. METHODS: We studied the squat movements of six healthy knees and measured point to point footprint distance. The footprint distances were measured after changing them to be 10% lower, 10% shallower, and both 10% lower and shallower than the defined anatomical femoral footprint. RESULTS: Average length changes of 12.0 and 14.1 mm from maximum extension (10°) to deep flexion (150°) were observed when the anteromedial and posterolateral bundles were defined by the default anatomical position. Maximum and minimum length were reached during full extension and flexion for both the anteromedial and posterolateral bundles, respectively. At 10% lower, length increased 2.2 mm over the default value in both the anteromedial and posterolateral lengths. At 10% shallower, decreases of 4.1 mm and 3.9 mm were observed compared with the default anteromedial and posterolateral lengths, respectively. In the 10% lower and 10% shallower position, anteromedial and posterolateral lengths decreased 2.1 mm and 1.9 mm compared with the default value, respectively. CONCLUSIONS: The anteromedial and posterolateral bundles have a complementary role. Femoral footprint position defined in the lower direction leads to stronger tension during extension, while the higher and shallower direction leads to isometry during flexion, and the deeper direction leads to laxity during flexion. The target bone tunnel position is that the anteromedial bundle should not to be too low and too deep to maintain function of bundle with less change in length. In addition, the posterolateral bundle should be somewhat lower and/or deeper than the anteromedial, with the expectation that it will function to induce stronger tension at the extended position. However, we should avoid lower position when we cannot prepare a sufficient diameter of reconstructed bundle to avoid re-injury due to excessive tension.

A double-blind, placebo-controlled, randomised clinical study of the effect of pork collagen peptide supplementation on atherosclerosis in healthy older individuals.

We examined whether baPWV could be affected by pork collagen peptide (CP) ingestion. Seventy subjects were randomized into two groups (2.5 g/day CP and 2.5 g/day placebo). A significant reduction in baPWV was observed in the CP group compared to the placebo group. This study demonstrated that pork CP may contribute to the prevention of atherosclerosis in elderly.

Assessment of the midflexion rotational laxity in posterior-stabilized total knee arthroplasty.

PURPOSE: To evaluate changes in midflexion rotational laxity before and after posterior-stabilized (PS)-total knee arthroplasty (TKA). METHODS: Twenty-nine knees that underwent PS-TKA were evaluated. Manual mild passive rotational stress was applied to the knees, and the internal-external rotational angle was measured automatically by a navigation system at 30°, 45°, 60°, and 90° of knee flexion. RESULTS: The post-operative internal rotational laxity was statistically significantly increased compared to the preoperative level at 30°, 45°, 60°, and 90° of flexion. The post-operative external rotational laxity was statistically significantly decreased compared to the preoperative level at 45° and 60° of flexion. The post-operative internal-external rotational laxity was statistically significantly increased compared to the preoperative level only at 30° of flexion. The preoperative and post-operative rotational laxity showed a significant correlation at 30°, 45°, 60°, and 90° of flexion. CONCLUSION: Internal-external rotational laxity increases at the initial flexion range due to resection of both the anterior or posterior cruciate ligaments and retention of the collateral ligaments in PS-TKA. Preoperative and post-operative rotational laxity indicated a significant correlation at the midflexion range. This study showed that a large preoperative rotational laxity increased the risk of a large post-operative laxity, especially at the initial flexion range in PS-TKA. LEVEL OF EVIDENCE: III.

Varus-valgus stability at 90° flexion correlates with the stability at midflexion range more widely than that at 0° extension in posterior-stabilized total knee arthroplasty.

INTRODUCTION: Midflexion stability can potentially improve the outcome of total knee arthroplasty (TKA). The purpose of this study was to evaluate the correlation between varus-valgus stability at 0° of extension and 90° of flexion and that at the midflexion range in posterior-stabilized (PS)-TKA. MATERIALS AND METHODS: Forty-three knees that underwent PS-TKA were evaluated. Manual mild passive varus-valgus stress was applied to the knees, and the postoperative maximum varus-valgus stability was measured every 10° throughout range of motion, using a navigation system. Correlations between the stability at 0°, 90° of flexion, and that at each midflexion angle were evaluated using Spearman's correlation coefficients. RESULTS: The stability of 0° modestly correlated with that of 10°-20°, but it did not significantly correlate with that of 30°-80°. However, the stability of 90° strongly correlated with that of 60°-80°, modestly correlated with that of 40°-50°, weakly correlated with that of 20°-30°, and did not correlate with that of 10°. CONCLUSIONS: The present study confirmed the importance of acquiring stability at 90° flexion to achieve midflexion stability in PS-TKA. However, initial flexion stability did not strongly correlate with the stability at either 0° or 90°. Our findings can provide useful information for understanding varus-valgus stability throughout the range of motion in PS-TKA. Attention to soft tissue balancing is necessary to stabilize a knee at the initial flexion range in PS-TKA.

The influence of tibial resection on the PCL in PCL-retaining total knee arthroplasty: A clinical and cadaveric study.

BACKGROUND: The influence of tibial resection on the joint gap and on stability against posterior laxity in posterior cruciate ligament-retaining total knee arthroplasty (CR-TKA) remains unclear. In addition, there are no detailed reports regarding how much of the tibial attachment of the posterior cruciate ligament (PCL) is preserved during tibial resection. Our goals were to evaluate the influence of tibial resection on the intraoperative joint gap and on postoperative anteroposterior stability in a clinical population, and to assess the preserved area of the tibial PCL attachment using cadaveric knees. METHODS: In 20 consecutive patients, the joint gaps before and after tibial resection at 90° flexion and full extension were analyzed during CR-TKA, and anteroposterior stability was evaluated postoperatively. In 11 cadaveric knees, tibial resection with a thickness of 8, 10, 12, or 14 mm and a posterior slope of 3, 4, 5, 6, or 7° was simulated using computed tomography images, and the percentage of the preserved area of the attachment was calculated. RESULTS: The flexion gaps before and after tibial resection were 18.1 ± 1.9 mm and 18.4 ± 2.2 mm, respectively, with no statistically significant difference (p = 0.08). Similarly, the extension gap did not increase significantly before and after tibial resection (20.8 ± 2.5 mm and 21.0 ± 2.6 mm; p = 0.45). All knees maintained anteroposterior stability at the follow-up period (32.0 ± 1.9 months). The posterior slope of the tibial resection was 5.9 ± 1.4°, and the thickness of the lateral tibial resection was 10.4 ± 1.1 mm. The cutoffs to preserve more than 50% of the attachment were 10-mm thickness and 5° slope. CONCLUSIONS: Our results showed that tibial resection did not influence the intraoperative joint gap or postoperative anteroposterior stability. However, our analysis demonstrated that increased amounts of tibial resection led to considerable damage to the attachment.

Short-Term Study of the Outcome of a New Instrument for All-Inside Double-Bundle Anterior Cruciate Ligament Reconstruction.

PURPOSE: The purpose of this study was to evaluate the short-term clinical results and location of the bone tunnel with a new surgical procedure for all-inside double-bundle anterior cruciate ligament (ACL) reconstruction. METHODS: The double-bundle ACL reconstruction procedure was performed in 24 patients (13 male and 11 female patients) with a mean age of 31.0 years. Anterior and posterior tibial translation using an arthrometer (KT-1000; MEDmetric, San Diego, CA) and the Lysholm score were measured before surgery and at a mean of 24.8 months (range, 13 to 45 months) postoperatively. Computed tomography scans were taken to evaluate the bone tunnel positions using 3-dimensional images with the quadrant method for the femoral tunnel and Stäubli's technique for the tibial tunnel. RESULTS: Three-dimensional computed tomography scans showed that the anteromedial and posterolateral tunnels were placed in anatomically appropriate positions. Arthrometric measurements showed that the mean side-to-side differences were 5.3 mm (SD, 1.6 mm) preoperatively and 0.05 mm (SD, 0.7 mm) at a mean of 24.8 months postoperatively, indicating a remarkable improvement (P < .00001). The mean Lysholm score was 56.3 points (SD, 14.8 points) preoperatively and 95.5 points (SD, 3.8 points) at final follow-up and was significantly improved after the operation (P < .00001). CONCLUSIONS: The all-inside double-bundle ACL reconstruction technique used in this study resulted in the creation of tunnels in an anatomically appropriate position. Short-term clinical follow-up showed improvement in patient-reported outcomes and knee stability. This technique may provide an alternative option for all-inside ACL reconstruction. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Rotational Soft-Tissue Balance Is Highly Correlated with Rotational Kinematics in Total Knee Arthroplasty.

Recovery of normal knee kinematics is critical for improving functional outcomes and patient satisfaction after total knee arthroplasty (TKA). The kinematics pattern after TKA varies from case to case, and it remains unclear how to reproduce normal knee kinematics. The present study aimed to evaluate rotational knee kinematics and soft-tissue balance using a navigation system and to assess the influence of intraoperative soft-tissue balance on the rotational knee kinematics. We evaluated 81 osteoarthritic knees treated with TKA using a posterior stabilized (50 knees) or cruciate retaining (31 knees) prosthesis. Rotational kinematics were assessed at 0, 30, 45, 60, and 90 degrees flexion angles by using a computer-assisted navigation system. Correlation between femorotibial rotational position and measured soft tissue balance was assessed by using Spearman's rank correlation coefficient. Rotational soft-tissue balance (the median angle of rotational stress) was significantly correlated with rotational kinematics (rotational axis of the femur relative to the tibia throughout the range of motion) at all measured angles after TKA. The correlation coefficients between the median angle of rotational stress and rotational kinematics were 0.97, 0.80, 0.74, 0.71, and 0.70 at 0, 30, 45, 60, and 90 degrees of flexion, respectively (p-values <0.0001 in all measured angles). The correlation coefficient increased as the knee approached full extension. Our findings suggest that soft-tissue balance is a key factor for rotational kinematics, following both cruciate-retaining and posterior-stabilized TKA.

Femoral head translation in borderline and definite dysplastic hips during weight-bearing: 2D/3D image registration analysis.

PURPOSE: The aims of this study were to 1) assess femoral head translation during weight-bearing in symptomatic developmental dysplasia of the hip (DDH) and 2) compare it between borderline DDH and definite DDH. METHODS: The study included four individuals with borderline DDH and nine with definite DDH, scheduled for periacetabular osteotomy. Anteroposterior X-ray images of the hip joint were obtained in the standing position, and computed tomography images of the pelvis were obtained in the supine position. Femoral head translation from the supine to a standing position was measured using 2D/3D X-ray image registration. RESULTS: From a supine to a standing position, the femoral head translated 0.3 mm laterally, 0.5 mm anteriorly, and 0.5 mm superiorly on average. The mean femoral head translation in 3D between the supine and standing positions was 1.5 mm. The 3D femoral head translation in the borderline DDH group was significantly greater than that in the definite DDH group. In the definite DDH group, there was a significant correlation between the center edge (CE) angle and 3D femoral head translation (ρ = -0.78, P = 0.012). CONCLUSIONS: Symptomatic DDH showed femoral head translation in the anterior, lateral, and superior directions during weight-bearing. In definite DDH, the amount of femoral head translation was negatively correlated with the CE angle. The amount of 3D translation in patients with borderline DDH was larger than that in definite DDH. Dynamic joint instability during weight-bearing was observed in borderline DDH as well as definite DDH. Treatment to enhance joint stability during weight-bearing is important in both cases.

Difference in implant design affects midflexion rotational laxity in cruciate-retaining total knee arthroplasty: a computer navigation study.

PURPOSE: This study aimed to compare midflexion rotational laxity between two different design concept models of cruciate-retaining total knee arthroplasty: symmetrical surface design of neutral joint line obliquity and asymmetrical surface design of varus joint line obliquity. METHODS: Sixty-three knees that underwent cruciate-retaining total knee arthroplasty were evaluated. Manual maximum passive rotational stress without acceleration was applied to the knees under navigation monitoring. Pre-operative and post-operative internal and external rotational angles were measured at 30°, 45°, 60°, and 90° knee flexion. RESULTS: The post-operative internal rotational laxity was significantly increased compared with pre-operative levels at 30°, 45°, 60°, and 90° flexion among all subjects (mean 9.7° vs 11.1°, 10.6° vs 11.6°, 11.2° vs 12.9°, and 13.2° vs 14.9°; p = 0.01, 0.04, 0.001, and 0.008, respectively). The post-operative external rotational laxity was significantly decreased compared to pre-operative levels at 30°, 45°, 60°, and 90° flexion among all subjects (mean 10.8° vs 6.8°, 12.5° vs 9.4°, 12.8° vs 10.0°, and 11.3° vs 9.5°; p < 0.0001, < 0.0001, < 0.0001, and 0.0008, respectively). The post-operative total rotational laxity significantly decreased, compared with pre-operative levels, at 30° and 45° flexion among all subjects (mean 20.4° vs 17.9°, and 23.1° vs 21.1°; p = 0.002 and 0.04, respectively). The post-operative total rotational laxity was significantly smaller in asymmetrically designed total knee arthroplasty than in symmetrically designed total knee arthroplasty at 30°, 45°, and 60° flexion (mean 19.3° vs 15.8°, 22.8° vs 18.7°, and 24.4° vs 20.8°; p = 0.03, 0.03, and 0.02, respectively), whereas no significant difference was observed at 90° flexion. CONCLUSION: Compared to symmetrical surface design, asymmetrical surface design resulted in lower rotational laxity at the midflexion range in cruciate-retaining total knee arthroplasty. LEVEL OF EVIDENCE: III.

Psoriatic arthritis successfully treated with second-line anti-interleukin-6 treatment: a case report and review of the literature.

BACKGROUND: Psoriatic arthritis treatment with antitumor necrosis factor has been shown to reduce disease activity. Nonetheless, more than 30% of patients do not achieve a sufficient response to tumor necrosis factor blockers. Currently, treatment with interleukin-6 inhibitors is expected to be effective and suppress the joint destruction in patients with psoriatic arthritis; however, evidence regarding their efficacy is limited to a few reports. CASE PRESENTATION: A 78-year-old Japanese woman with psoriatic arthritis associated with rapid joint destruction was successfully treated with a second-line anti-interleukin-6 receptor agent. In this case, a tumor necrosis factor inhibitor induced an inadequate response, and the right knee and left hip joints required artificial joint replacement surgery. However, second line treatment with anti-interleukin-6 treatment was effective, and the right elbow joint function was preserved. CONCLUSIONS: We experienced a case of psoriatic arthritis, in which anti-interleukin-6 treatment repaired a bone cyst in the lateral epicondyle of the humerus and enthesitis of the distal interphalangeal joints. The patient is currently in clinical remission with no restrictions in daily life activities. Anti-interleukin-6 treatment may address the unmet needs of patients with psoriatic arthritis who are resistant or intolerant to antitumor necrosis factor treatment, with rapidly destructive large joints but with well-managed skin manifestations.

Gender-specific difference in the recurrence of flexion contracture after total knee arthroplasty.

BACKGROUND: Range of motion after total knee arthroplasty (TKA) can impact patients' daily lives. Nevertheless, flexion contracture (FC) often recurs after TKA, even upon achieving full extension intraoperatively. This study aimed to evaluate the relationship among preoperative, intraoperative, and postoperative knee extension angles, and clarify the risk factor for postoperative FC. METHODS: One hundred forty-seven knees undergoing TKA using a navigation system were evaluated. We measured the pre- and postoperative (6 months after TKA) extension angles using a goniometer, and intraoperative (before and after TKA) extension angle using a navigation system; the correlation between these angles at each time point was evaluated. RESULTS: The mean preoperative, intraoperative (before and after TKA) and postoperative extension angles were -9.9°, -6.8°, -0.1°, and -2.0°. Regarding intraoperative extension angle after TKA, 58 knees showed ≤ 5° hyperextension and six knees showed > 5° hyperextension. At 6 months, no cases showed hyperextension and 105 knees showed full extension. The mean intraoperative extension angle after TKA in the postoperative full extension group was 0.4°. A significant correlation was found among extension angles at each point (p<0.01, respectively). However, the intraoperative extension angle after TKA correlated with the postoperative extension angle only in females. Contrarily, the recurrence rate of FC was significantly higher in males than in females (p<0.01). CONCLUSION: Intraoperative extension angles significantly correlated with pre- and postoperative extension angles in TKA. Moreover, intraoperative mild (≤ 5°) hyperextension is acceptable for postoperative full extension. There was a gender-specific difference in correlation between intra- and postoperative knee extension angles. LEVEL OF EVIDENCE: III.

Efficacy of posterior capsular release for flexion contracture in posterior-stabilized total knee arthroplasty.

PURPOSE: Posterior capsular contracture causes stiffness during knee extension in knee osteoarthritis. Furthermore, in posterior-stabilized total knee arthroplasty (PS-TKA), a unique design such as the cam mechanism could conflict with the posterior capsule (PC) causing flexion contracture (FC). However, few studies have focused on the anatomical aspects of the PC. This study aimed to investigate the anatomical site and forms of posterior capsular attachment to the femoral cortex, and to evaluate the efficacy of posterior capsular release for FC by assessing changes in knee extension angles using a navigation system. METHODS: Attachment sites of the PC were investigated in 10 cadaveric knees using computed tomography. PS-TKA was performed in six cadaveric knees using a navigation system to evaluate the efficacy of posterior capsular release for FC. Posterior capsular release was performed stepwise at each part of the femoral condyle. RESULTS: The gastrocnemius tendon and PC were integrally attached to the femoral cortex at the medial and lateral condyles, whereas the PC at the intercondylar fossa was independently attached directly to the femoral cortex. Moreover, the PC at the intercondylar fossa was attached most distally among each femoral condyle. Posterior capsular release at the intercondylar fossa allowed 11.4° ± 2.8° improvement in knee extension. This angle was further improved by 5.5° ± 1.3°, after subsequent capsular release at the medial and lateral condyles. CONCLUSION: The forms and sites of posterior capsular attachment differed based on the part of the femoral condyle. Stepwise posterior capsular release was effective for FC in PS-TKA. LEVEL OF EVIDENCE: III.

Bi-cruciate substituting total knee arthroplasty provides varus-valgus stability throughout the midflexion range.

BACKGROUND: Proper soft tissue balance is crucial for a successful clinical outcome after total knee arthroplasty (TKA). Bi-cruciate substituting (BCS)-TKA has been developed to more closely approximate normal knee characteristics. The purpose of the present study was to evaluate midflexion laxity before and after BCS-TKA using a navigation system, and assess the correlation between intraoperative laxity and the maximum flexion angle after surgery. METHODS: Fifty-one knees in 46 patients with osteoarthritis replaced with BCS prosthesis were assessed. Manual mild passive internal-external rotational and varus-valgus stress was applied to the knees, and the maximum total laxity was measured automatically by a navigation system before and after TKA. The correlations with the range of motion (ROM) were evaluated using Spearman's correlation coefficients (ρ). RESULTS: Internal-external stress assessment revealed no statistically significant difference at each flexion angle before and after BCS-TKA. In contrast, the varus-valgus stress assessment revealed that BCS-TKA had significantly decreased varus-valgus laxity from preoperative levels at 20-120° flexion angles. Furthermore, the maximum flexion angle at six months after surgery significantly correlated with the intraoperative laxity at deep flexion range. CONCLUSION: BCS-TKA stabilized varus-valgus laxity to better than preoperative levels at midflexion range.

Preoperative varus-valgus kinematic pattern throughout flexion persists more strongly after cruciate-retaining than after posterior-stabilized total knee arthroplasty.

BACKGROUND: Restoration of normal knee kinematics is key to improving patient satisfaction and functional outcomes after total knee arthroplasty (TKA). However, the effect of preoperative varus-valgus kinematics due to knee osteoarthritis on the postoperative kinematics is unclear. The function of the knee ligament contributes to both knee stability and kinematics. The aim of this study was to evaluate changes in varus-valgus kinematics before and after TKA using a navigation system, in addition to comparing the pre- and postoperative changes in kinematic patterns between cruciate-retaining (CR)- and posterior-stabilized (PS)-TKAs. METHODS: Forty knees treated with TKA were evaluated (CR-TKA 20; PS-TKA 20). Manual mild passive knee flexion was applied while moving the leg from full extension to flexion. The varus-valgus angle was automatically measured by a navigation system at every 10° of the flexion angle, and the kinematics were evaluated. RESULTS: Kinematic patterns throughout flexion can be classified into five types. The pre- and postoperative kinematic patterns were similar in 60% of patients who underwent CR-TKA, whereas they were similar in only 25% of those who underwent PS-TKA. The mean change in the size of the varus-valgus angle throughout flexion did not differ between CR-TKA and PS-TKA. However, the distribution of changes in the size of the varus-valgus angle differed between CR-TKA and PS-TKA. CONCLUSIONS: We obtained the following results: 1) some patterns of varus-valgus kinematics are noted under unloading conditions despite recovery of neutral alignment in extension and 2) the preoperative varus-valgus kinematic pattern persisted more strongly after CR-TKA than after PS-TKA.

Fibronectin regulates proteoglycan production balance in transforming growth factor-ß1-induced chondrogenesis.

Transforming growth factor (TGF)-ß and bone morphogenetic protein (BMP) induce a cartilage-specific extracellular matrix (ECM) gene, aggrecan, in a chondrogenic cell line, ATDC5. The results of our recent study show that TGF-ß1, but not BMP-4, strongly induces an ECM gene, fibronectin, during chondrogenesis. However, the role of fibronectin in chondrogenesis is unclear. In the current study, our results showed that TGF-ß1, but not BMP-4, led to versican-dominant proteoglycan production during chondrogenesis of ATDC5 cells. siRNA-mediated reduction of fibronectin and interference in the liaison between fibronectin and integrins by the Arg-Gly-Asp-Ser (RGDS) peptide increased aggrecan expression, and decreased versican expression by TGF-ß1 stimulation. These data suggest that fibronectin is a critical mediator for TGF-ß-specific production balance of 2 major proteoglycans, aggrecan and versican, during chondrogenesis.