Andrew J. Cosgarea

Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-β1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-β1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-β1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-β activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-β type II receptor (TβRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-β1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach.

Technical Errors During Medial Patellofemoral Ligament Reconstruction Could Overload Medial Patellofemoral Cartilage A Computational Analysis

Background The influence of reconstruction of the medial patellofemoral ligament on the patellofemoral force and pressure distributions has not yet been investigated. Hypothesis Technical errors can cause tension to develop within a reconstructed medial patellofemoral ligament, which will adversely alter the normal patellofemoral force distribution by increasing the load applied to the medial cartilage. Study Design Controlled laboratory study. Methods Four computational knee models were used to simulate knee function from 30° to 90° of flexion with (1) an intact medial patellofemoral ligament, (2) an anatomically correct reconstruction using a double hamstring tendon autograft, (3) a 5-mm proximally malpositioned femoral attachment site, (4) a graft that is 3 mm shorter than the intact medial patellofemoral ligament, and (5) combined proximal malpositioning and a short graft. Results The results were similar for the intact and anatomically reconstructed medial patellofemoral ligament. Proximal malpositioning of the femoral attachment and using a short graft increased the graft tension during flexion, which decreased the lateral force and the lateral tilt moment acting on the patella. When a short graft was combined with proximal malpositioning, the compressive force applied to the medial cartilage at least doubled at low flexion angles, which increased the peak medial pressure by more than 50% at low flexion angles. Conclusion When the medial patellofemoral ligament is reconstructed, small errors in graft length and position can dramatically increase the force and pressure applied to medial patellofemoral cartilage. Clinical Relevance Overloading the medial cartilage after medial patellofemoral ligament reconstruction could lead to degradation, pain, and arthrosis.

Clinical features of the different types of SLAP lesions: An analysis of one hundred and thirty-nine cases

Background: Previous studies have suggested that SLAP (superior labrum anterior posterior) lesions are a distinct clinical entity. The goals of this study were to define the prevalence, associated pathological findings, and clinical features of the different types of SLAP lesions with use of a common classification system.Methods: Five hundred and forty-four patients undergoing shoulder arthroscopy for a variety of diagnoses were prospectively included in this consecutive case series. SLAP lesions were grouped with use of the Snyder classification. Demographic data, clinical data, and arthroscopic findings in the groups with SLAP lesions were compared with those in a control group with no SLAP lesion.Results: Of 544 shoulder arthroscopy procedures, 139 (26%) demonstrated a SLAP lesion. One hundred and three (74%) of the SLAP lesions were Type I, twenty-nine (21%) were Type II, one (0.7%) was Type III, and six (4%) were Type IV. Most (123) of the SLAP lesions were found to be associated with other intra-articular lesions. Multivariate analysis revealed that a positive Speed test and a supraspinatus tear were significantly associated with Type-I lesions (p = 0.012 and p = 0.001, respectively). The findings associated with Type-II lesions differed according to the patients age: Type-II lesions in patients who were forty years of age or younger were associated only with a Bankart lesion, whereas those in patients older than forty years of age were associated with a supraspinatus tear and osteoarthritis of the humeral head. Type-III and Type-IV lesions were associated with a high-demand occupation and a Bankart lesion.Conclusions: This study demonstrated that the prevalence, associated pathological findings, and clinical features of the different types of SLAP lesions vary with the patient population that is studied. Also, the clinical features and pathological findings associated with the different types of SLAP lesions often overlap. Isolated SLAP lesions with no associated pathological findings are uncommon, and care must be taken when ascribing symptoms to a SLAP lesion when other lesions are present.Level of Evidence: Diagnostic study, Level IV-1 (case-control study). See p. 2 for complete description of levels of evidence.

Q-angle influences tibiofemoral and patellofemoral kinematics.

Numerous surgical procedures have been developed to correct patellar tracking and improve patellofemoral symptoms by altering the Q‐angle (the angle between the quadriceps load vector and the patellar tendon load vector). The influence of the Q‐angle on knee kinematics has yet to be specifically quantified, however. In vitro knee simulation was performed to relate the Q‐angle to tibiofemoral and patellofemoral kinematics. Six cadaver knees were tested by applying simulated hamstrings, quadriceps and hip loads to induce knee flexion. The knees were tested with a normal alignment, after increasing the Q‐angle and after decreasing the Q‐angle. Increasing the Q‐angle significantly shifted the patella laterally from 20° to 60° of knee flexion, tilted the patella medially from 20° to 80° of flexion, and rotated the patella medially from 20° to 50° of flexion. Decreasing the Q‐angle significantly tilted the patella laterally at 20° and from 50° to 80° of flexion, rotated the tibia externally from 30° to 60° of flexion, and increased the tibiofemoral varus orientation from 40° to 90° of flexion. The results show that an increase in the Q‐angle could lead to lateral patellar dislocation or increased lateral patellofemoral contact pressures. A Q‐angle decrease may not shift the patella medially, but could increase the medial tibiofemoral contact pressure by increasing the varus orientation.

Prevention of Arthrofibrosis After Anterior Cruciate Ligament Reconstruction Using the Central Third Patellar Tendon Autograft

A retrospective analysis was performed to explain the decreasing incidence of postoperative arthrofibrosis of the knee in 191 consecutive patients who had anterior cruciate ligament reconstruction using the central third patellar tendon from 1987 through 1991. Follow-up data were available on 188 patients (98%). Age, sex, time interval from injury, preoperative motion, and concomi tant meniscal repair or partial meniscectomy were evaluated for their significance as risk factors. Twenty- two of 188 patients (12%) developed arthrofibrosis; the incidence was lower when the acute anterior cruciate ligament reconstruction was delayed at least 3 weeks from the injury, and when preoperative extension was 10° or better. Age, sex, preoperative flexion, and need for concomitant meniscal surgery were not risk factors. The postoperative motion protocol evolved during the study period. Group 1 patients were braced in 45° of flexion for 1 week before passive extension was al lowed. In Group 2, motion was started after 48 hours. Group 3 patients were braced in full extension, with mo tion starting within 24 hours. With these changes, the incidence dropped from 23% to 3%. Decreases in the incidence of arthrofibrosis with modifications in opera tive technique and postoperative analgesia were not statistically significant.

The Surgical Treatment of Arthrofibrosis of the Knee

Sixty-one lysis of adhesion procedures were performed for arthrofibrosis of the knee between 1981 and 1990. In 43 cases (37 patients) the etiology was prior knee ligament surgery. Ten cases had sustained fractures about the knee and eight had miscellaneous etiologies. Six patients required a second lysis of adhesion pro cedure. A retrospective analysis of the 43 ligament pa tients was undertaken to evaluate the results of surgical treatment. All 43 cases were available for followup at an average of 3.6 years. Surgical indications included flex ion or extension deficits of ≥10° or when motion failed to improve despite 2 months of intense therapy. Follow-up assessment included clinical and radio graphic evaluation. Flexion improved from 83% to 97% of the contralateral side. Extension deficits improved from 14° to 3°. Only 23 of 37 patients (62%) achieved satisfactory functional results. Radiographic evidence of degenerative changes, soft tissue calcification, and patella infera was found in 89%, 51 %, and 9% of the patients, respectively. Patients requiring surgical treat ment for arthrofibrosis after knee ligament surgery achieved excellent motion gains, but functional out come scores were compromised and radiographic find ings were concerning. Patients with the localized an terior intraarticular variant or those undergoing lysis of adhesion surgery sooner than 6 months had outcomes comparable with controls.

Evaluation of a computational model used to predict the patellofemoral contact pressure distribution.

One possible cause of patellofemoral pain syndrome is excessive lateral force acting on the patella. Although several treatment methods focus on decreasing the lateral force acting on the patella, the relationship between the lateral force and the patellofemoral contact pressure distribution is unclear. A computational model has been developed to determine how loading variations alter the patellofemoral force and pressure distributions for individual knees. The model allows variation in the quadriceps and patella tendon forces, and calculates the predicted contact pressure distribution using the discrete element analysis technique. To characterize the accuracy of the model, four cadaver knees were flexed on a knee simulator with three initial Q-angles, while recording the force and pressure distributions with a pressure sensor. A model of each knee was created from CT data. Using the external force applied to the knee, the geometry of the knee, and the quadriceps origin as input, the pressure distribution was calculated during flexion. Similar trends were noted for the computational and experimental results. The percentage of the total force applied to the lateral cartilage increased with the Q-angle. The maximum contact pressure increased during flexion. The maximum lateral contact pressure increased with the Q-angle for three knees. For the other knee, increasing the Q-angle decreased the maximum lateral pressure. The maximum medial contact pressure decreased as the Q-angle increased. By characterizing the influence of patellofemoral loading on the force and pressure distributions, the computational model could be used to evaluate treatment methods prescribed for patellofemoral pain.

Neurovascular Complications of Knee Arthroscopy

During the last 3 decades, arthroscopy has revolutionized the way knee surgery is performed. The indications and the applications of arthroscopic procedures in the knee joint have enormously increased with the improvement in surgical technique and advent of new arthroscopic equipment. The use of arthroscopic techniques has led to a significant decrease in morbidity for the patient with intraarticular abnormalities, in terms of both diagnosis and surgical correction. Even though knee arthroscopy is a minimally invasive procedure with relatively low morbidity, it is not without risk of complications, of which neurovascular complications are among the most serious and devastating. The reported incidence of neurovascular complication is low, but it may be underestimated. Many neurovascular complications that occur are preventable with a thorough understanding of neurovascular anatomy, good preoperative and intraoperative planning, and attention to the details of basic techniques and the equipment used for the procedure. It is imperative that the surgeon who is performing arthroscopy be aware of these neurovascular complications, recognize them as early as possible, and initiate further evaluation and treatment as expeditiously as possible. In this article, the causes, management, prevention, and medicolegal implications of neurovascular complications of knee arthroscopy are reviewed.

The Soleus Muscle Acts as an Agonist for the Anterior Cruciate Ligament An In Vitro Experimental Study

Background: Although the quadriceps muscles are known antagonists for the anterior cruciate ligament and the hamstring muscles are known agonists, the influence of the calf muscles on knee stability is not well understood. Hypothesis: The soleus muscle acts as an anterior cruciate ligament agonist and the gastrocnemius muscle acts as an anterior cruciate ligament antagonist. Study Design: Controlled laboratory study. Methods: Six cadaveric knees were tested with individual and combined activation of the gastrocnemius and soleus muscles to determine the influence of simulated muscle contraction on tibiofemoral motion. Results: At all flexion angles, applying the soleus muscle force tended to translate the tibia posteriorly, whereas applying the gastrocnemius muscle force tended to translate the tibia anteriorly. Applying the soleus and gastrocnemius muscle forces together also tended to translate the tibia anteriorly. The average anterior and posterior tibial translations were greatest at 50° of flexion. Conclusions: The soleus muscle is capable of acting as an agonist for the anterior cruciate ligament and the gastrocnemius muscle can act as an antagonist. Clinical Relevance: A better understanding of the agonistic behavior of the soleus muscle on the anterior cruciate ligament may lead to the development of training and rehabilitation strategies that could reduce the incidence of injury and improve function in both patients with anterior cruciate ligament deficiency and patients who have undergone anterior cruciate ligament reconstruction.

Posterior cruciate ligament rupture alters in vitro knee kinematics.

Isolated posterior cruciate ligament injuries usually are treated nonoperatively, although some patients remain symptomatic, and degenerative changes within the patellofemoral joint and the medial compartment of the tibiofemoral joint have been seen in followup studies. In vitro simulation of knee squatting was done to quantify the influence of the posterior cruciate ligament on tibiofemoral and patellofemoral kinematics. For five knee specimens, knee kinematics were measured before and after sectioning the posterior cruciate ligament, and compared using a Wilcoxon signed rank test. The only kinematic parameters that changed significantly after sectioning the posterior cruciate ligament were the tibial posterior translation and patellar flexion. The posterior translation of the tibia increased significantly between 25° and 90° flexion. The average increase in the posterior translation exceeded 10 mm at 90° flexion. The patellar flexion increased significantly from 30° to 90° flexion. The average patellar flexion increase peaked at 4.4° at 45° flexion. Increased tibial translation could adversely influence joint stability. Increased patellar flexion could increase the patellofemoral joint pressure, especially at the inferior pole, leading to degenerative changes within the patellofemoral joint.