The Association of Variants within Types V and XI Collagen Genes with Knee Joint Laxity Measurements.

Joint laxity is a multifactorial phenotype with a heritable component. Mutations or common polymorphisms within the α1(V) (COL5A1), α1(XI) (COL11A1) and α2(XI) (COL11A2) collagen genes have been reported or proposed to associate with joint hypermobility, range of motion and/or genu recurvatum. The aim of this study was to investigate whether polymorphisms within these collagen-encoding genes are associated with measurements of knee joint laxity and computed ligament length changes within the non-dominant leg. One hundred and six healthy participants were assessed for genu recurvatum (knee hyperextension), anterior-posterior tibial translation, external-internal tibial rotation and ligament length changes during knee rotation of their non-dominant leg. Participants were genotyped for COL5A1 rs12722 (T/C), COL11A1 rs3753841 (C/T), COL11A1 rs1676486 (T/C) and COL11A2 rs1799907 (A/T). The genotype-genotype combination of any two or more of the four COL5A1 rs12722 CC, COL11A1 rs3753841 CC, COL11A1 rs1676486 TT and COL11A2 rs1799907 AA genotypes was associated with decreased active and passive knee hyperextension. These genotype-genotype combinations, including sex (male), increased age and decreased body mass collectively, also contributed to decreased passive knee hyperextension. These findings suggest that COL5A1, COL11A1 and COL11A2 gene-gene interactions are associated with knee hyperextension measurements of the non-dominant leg of healthy individuals.

Investigating the association between COL1A1 and COL3A1 gene variants and knee joint laxity and ligament measurements.

BACKGROUND: Joint laxity is a multifactorial phenotype with a heritable component. Type I collagen gene (COL1A1) mutations cause connective tissue disorders with joint hypermobility as a clinical feature, while variants within COL1A1 and type III collagen gene (COL3A1) are associated with musculoskeletal injuries. The aim of this study was to investigate whether COL1A1 and COL3A1 variants are associated with measurements of non-dominant knee joint laxity and computed ligament length changes. METHODS: 106 moderately active uninjured participants were assessed for genu recurvatum, anterior-posterior tibial translation, external-internal tibial rotation and calculated ligament length changes during knee rotation. Participants were genotyped for COL1A1 rs1107946, rs1800012 and COL3A1 rs1800255. FINDINGS: The COL1A1 rs1107946 GG genotype had significantly larger external rotation [GG: 5.7° (4.9°;6.4°) vs GT: 4.6° (4.2°;5.5°), adjusted P = 0.014], internal rotation [GG: 5.9° (5.3°;6.6°) vs GT: 5.4° (4.7°;6.2°), adjusted P = 0.014], and slack [GG: 18.2° ± 3.2° vs GT: 16.1° ± 3.1°, adjusted P = 0.014]. The GG genotype at both COL1A1 variants had significantly larger active displacement [GG + GG: 6.0 mm (3.8 mm;8.0 mm) vs other genotype combinations: 4.0 mm (2.5 mm;6.0 mm), P < 0.001] and maximum displacement [GG + GG: 8.0 mm (6.9 mm;10.6 mm) vs other genotype combinations: 6.0 mm (5.0 mm;9.0 mm), P = 0.003]. COL1A1 rs1107946 significantly contributed to increased external and internal rotation in multilinear regression models, while both COL1A1 variants, significantly contributed to increased active displacement and slack. Larger medial and lateral cruciate ligament length changes were reported in participants with GG genotypes at both COL1A1 variants. INTERPRETATION: These findings suggest that the COL1A1 variants are associated with knee rotational laxity and changes in ligament length.

Efficacy of high-intensity home mechanical stretch therapy for treatment of shoulder stiffness: a retrospective review.

BACKGROUND: Shoulder stiffness resulting in motion loss can be caused by numerous conditions, the most common of which is adhesive capsulitis. Surgical intervention is often necessary when conservative methods fail. High-intensity stretch (HIS) treatment may be able to provide increased motion gains while avoiding the cost and complications of surgery. OBJECTIVES: The purpose of this study was to review data from patients who were prescribed a HIS device to recover their shoulder motion to determine the efficacy of the device. The hypotheses were that patients would achieve significant range of motion (ROM) gains and that ROM would increase to a level at which patients would be able to avoid a motion loss surgery and perform activities of daily living. METHODS: Clinical notes were reviewed for patients whose progress plateaued after 4 weeks of therapy and were subsequently prescribed the HIS device after failing to meet their treatment goals. ROM data were recorded for external rotation, abduction, forward flexion, and internal rotation. Pre- and post-treatment ROM data were compared using t-tests. RESULTS: Significant ROM gains were seen in all planes of motion (p < 0.001). Patients gained an average of 29.9° in external rotation with a last recorded rotation of 59.2°. In abduction, patients gained 40.5° with a last recorded abduction of 123.3°. In forward flexion, patients gained 30.3° with a last recorded flexion of 138.7°. In internal rotation, patients gained 15.2° with a last recorded rotation of 57.6°. These last recorded ranges of motion were sufficient to perform nearly all activities of daily living. CONCLUSIONS: The HIS device was effective in treating patients with shoulder motion loss as demonstrated by the significant ROM gains in all planes of motion. The ability for a patient to recover lost motion quickly without surgery is of great value to quality of life and in healthcare cost savings. We believe this high-intensity stretch device should be considered for use by patients who are at risk for a motion loss surgery.

Efficacy of non-operative treatment of patients with knee arthrofibrosis using high-intensity home mechanical therapy: a retrospective review of 11,000+ patients.

BACKGROUND: Recovery from knee surgery or injury can be hindered by knee arthrofibrosis, which can lead to motion limitations, pain and delayed recovery. Surgery or prolonged physical therapy are often treatment options for arthrofibrosis, but they can result in increased costs and decreased quality of life. A treatment option that can regain lost motion without surgery would help minimize risks and costs for the patient. The purpose of this study was to determine treatment efficacy of high-intensity home mechanical stretch therapy in patients with knee arthrofibrosis. METHODS: Records were reviewed for 11,000+ patients who were prescribed a high-intensity stretch device to regain knee flexion. Initial and last recorded knee flexion and days between measurements were available for 9842 patients (Dataset 1). Dataset 2 was a subset of 966 patients from Dataset 1. These 966 patients had separate more rigorous measurements available from physical therapy notes (Dataset 3) in addition to data from the internal database (Dataset 2). Within and between dataset statistics were calculated using t tests for comparison of means and Cohen's d for determination of effect size. RESULTS: All dataset showed significant gains in flexion (p < 0.01). Mean initial flexion, last recorded flexion and flexion gain were 79.5°, 108.4°, and 29.9°, respectively in Dataset 1. Differences between Datasets 2 and 3 had small effect sizes (Cohen's d < 0.17). The were no significant differences when comparing workers' compensation and non-workers' compensation patients. The average last recorded flexion for all datasets was above the level required to perform activities of daily living. Motion gains were recorded in under 60 days from device delivery. CONCLUSIONS: High-intensity home mechanical stretch therapy was effective in restoring knee flexion, generally in 2 months or less, and in avoiding additional surgery in severe motion loss patients regardless of sex, age, or workers' compensation status. We believe high-intensity stretching should be considered in any patient who is at risk for a secondary motion loss surgery, because in over 90% of these patients, the complications and costs associated with surgery can be avoided.

Reliability of a Robotic Knee Testing Tool to Assess Rotational Stability of the Knee Joint in Healthy Female and Male Volunteers.

BACKGROUND: Several clinical tests exist to assess knee laxity. Although these assessments are the predominant tools of diagnosis, they are subjective and rely on the experience of the clinician. The robotic knee testing (RKT) device has been developed to quantitatively and objectively measure rotational knee laxity. The purpose of this study was primarily to determine the intra-tester reliability of rotational knee laxity and slack, the amount of rotation occurring between the two turning points of the load deformation curve, measured by the RKT device and investigate the differences between female and male measurements. METHODS: Ninety-one healthy and moderately active volunteers took part in the study, of which twenty-five participated in the reliability study. Tibial rotation was performed using a servomotor to a torque of 6 N m, while measurements of motion in all 6° of freedom were collected. Reliability measurements were collected over 5 days at similar times of the day. Intra-class correlation coefficient (ICC) values and standard error of measurement (SEM) were determined across the load deformation curves. Linear mixed effects modelling was used to further assess the reliability of the measurement of external and internal tibial rotation using features of the curve (internal/external rotational laxity and slack). Measurements of internal/external rotational laxity and slack were compared between the sexes using the Student t test. RESULTS: Pointwise axial rotation measurements of the tibia had good reliability [ICC (2,1) 0.83-0.89], while reliability of the secondary motions ranged between poor and good [ICC (2,1) 0.31-0.89]. All SEMs were less than 0.3°. Most of the variation of the curve features were accounted for by inter-subject differences (56.2-77.8%) and showed moderate to good reliability. Comparison of the right legs of the sexes revealed that females had significantly larger amounts of internal rotation laxity (females 6.1 ± 1.3° vs males 5.6 ± 0.9°, p = 0.037), external rotation laxity (females 6.0 ± 1.6° vs males 5.0 ± 1.2°, p = 0.002) and slack (females 19.2 ± 4.2° vs males 16.6 ± 2.9°, p = 0.003). Similar results were seen within the left legs. CONCLUSIONS: Overall, the RKT is a reliable and precise tool to assess the rotational laxity of the knee joint in healthy individuals. Finally, greater amounts of laxity and slack were also reported for females.

STIP1/HOP Regulates the Actin Cytoskeleton through Interactions with Actin and Changes in Actin-Binding Proteins Cofilin and Profilin.

Cell migration plays a vital role in both health and disease. It is driven by reorganization of the actin cytoskeleton, which is regulated by actin-binding proteins cofilin and profilin. Stress-inducible phosphoprotein 1 (STIP1) is a well-described co-chaperone of the Hsp90 chaperone system, and our findings identify a potential regulatory role of STIP1 in actin dynamics. We show that STIP1 can be isolated in complex with actin and Hsp90 from HEK293T cells and directly interacts with actin in vitro via the C-terminal TPR2AB-DP2 domain of STIP1, potentially due to a region spanning two putative actin-binding motifs. We found that STIP1 could stimulate the in vitro ATPase activity of actin, suggesting a potential role in the modulation of F-actin formation. Interestingly, while STIP1 depletion in HEK293T cells had no major effect on total actin levels, it led to increased nuclear accumulation of actin, disorganization of F-actin structures, and an increase and decrease in cofilin and profilin levels, respectively. This study suggests that STIP1 regulates the cytoskeleton by interacting with actin, or via regulating the ratio of proteins known to affect actin dynamics.