Degraded RNA from Human Anterior Cruciate Ligaments Yields Valid Gene Expression Profiles.

Correlating gene expression patterns with biomechanical properties of connective tissues provides insights into the molecular processes underlying the tissue growth and repair. Cadaveric specimens such as human knees are widely considered suitable for biomechanical studies, but their usefulness for gene expression experiments is potentially limited by the unavoidable, nuclease-mediated degradation of RNA. Here, we tested whether valid gene expression profiles can be obtained using degraded RNA from human anterior cruciate ligaments (ACLs).

The Codon 72 Polymorphism Contributes to TSC Tumorigenesis through the Notch-Nodal Axis.

We discovered that 90.3% of patients with angiomyolipomas, lymphangioleiomyomatosis (LAM), and tuberous sclerosis complex (TSC) carry the arginine variant of codon 72 (R72) of and that R72 increases the risk for angiomyolipoma. R72 transactivates and better than the proline variant of codon 72 (P72); therefore, the expression of and is increased in angiomyolipoma cells that carry R72.

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate.

Liposomal nanoparticles are the most commonly used drug nano-delivery platforms. However, recent reports show that certain pegylated liposomal nanoparticles (PLNs) and polymeric nanoparticles have the potential to enhance tumor growth and inhibit antitumor immunity in murine cancer models. We sought herein to identify the mechanisms and determine whether PLN-associated immunosuppression and tumor growth can be reversed using alendronate, an immune modulatory drug.

Notch transactivates Rheb to maintain the multipotency of TSC-null cells.

Differentiation abnormalities are a hallmark of tuberous sclerosis complex (TSC) manifestations; however, the genesis of these abnormalities remains unclear. Here we report on mechanisms controlling the multi-lineage, early neuronal progenitor and neural stem-like cell characteristics of lymphangioleiomyomatosis (LAM) and angiomyolipoma cells. These mechanisms include the activation of a previously unreported Rheb-Notch-Rheb regulatory loop, in which the cyclic binding of Notch1 to the Notch-responsive elements (NREs) on the Rheb promoter is a key event.

Age, sex, body anthropometry, and ACL size predict the structural properties of the human anterior cruciate ligament.

Anterior cruciate ligament (ACL) injury continues to be at the forefront of sports injury concerns because of its impact on quality of life and joint health prognosis. One strategy is to reduce the occurrence of this injury by identifying at-risk subjects based on key putative risk factors. The purpose of our study was to develop models that predict the structural properties of a subject's ACL based on the combination of known risk factors.

Shallow medial tibial plateau and steep medial and lateral tibial slopes: new risk factors for anterior cruciate ligament injuries.

Background: The geometry of the tibial plateau has been largely ignored as a source of possible risk factors for anterior cruciate ligament injury. Discovering the anterior cruciate ligament injury risk factors associated with the tibial plateau may lead to delineation of the existing sex-based disparity in anterior cruciate ligament injuries and help develop strategies for the prevention of anterior cruciate ligament injuries regardless of gender.

Hypothesis: Individuals with a shallower medial tibial depth of concavity, while having increased posteriorly directed slope of their tibial plateau, are at increased risk of suffering an anterior cruciate ligament injury compared with those with decreased posterior slope and increased medial tibial depth.

The geometry of the tibial plateau and its influence on the biomechanics of the tibiofemoral joint.

Background: The geometry of the tibial plateau is complex and asymmetric. Previous research has characterized subject-to-subject differences in the tibial plateau geometry in the sagittal plane on the basis of a single parameter, the posterior slope. We hypothesized that (1) there are large subject-to-subject variations in terms of slopes, the depth of concavity of the medial plateau, and the extent of convexity of the lateral plateau; (2) medial tibial slope and lateral tibial slope are different within subjects; (3) there are sex-based differences in the slopes as well as concavities and convexities of the tibial plateau; and (4) age is not associated with any of the measured parameters.

The human anterior cruciate ligament: sex differences in ultrastructure and correlation with biomechanical properties.

The purpose of this study was to investigate the existence of sex-based differences in the ultrastructural characteristics of the human anterior cruciate ligament (ACL) as the underlying cause of differences in the structural and mechanical properties between sexes. The ACL of six male and six female cadaveric donors were randomly chosen from a pool of 10 male and 10 female ACLs that had previously been tested for their structural and mechanical properties. Eighteen tissue samples from the distal, proximal, and middle sections of the anteromedial and posterolateral bundles were analyzed by transmission electron microscopy.

Sex-based differences in the tensile properties of the human anterior cruciate ligament.

After immense amounts of research, the root cause for the significantly higher rates of anterior cruciate ligament (ACL) failure incidents in females as compared to males still remains unknown and the existing sex-based disparity has not diminished. To date, the possibility that the female ACL is mechanically weaker than the male ACL has not been directly investigated. Although it has been established in the literature that the female ACL is smaller in size, the differences in the structural and material properties of the ACL between sexes have not been studied.