Loss of myostatin (GDF8) function increases osteogenic differentiation of bone marrow-derived mesenchymal stem cells but the osteogenic effect is ablated with unloading.

Myostatin (GDF8) is a negative regulator of skeletal muscle growth and mice lacking myostatin show a significant increase in muscle mass and bone density compared to normal mice. In order to further define the role of myostatin in regulating bone mass we sought to determine if loss of myostatin function significantly altered the potential for osteogenic differentiation in bone marrow-derived mesenchymal stem cells in vitro and in vivo. We first examined expression of the myostatin receptor, the type IIB activin receptor (AcvrIIB), in bone marrow-derived mesenchymal stem cells (BMSCs) isolated from mouse long bones. This receptor was found to be expressed at high levels in BMSCs, and we were also able to detect AcvrIIB protein in BMSCs in situ using immunofluorescence. BMSCs isolated from myostatin-deficient mice showed increased osteogenic differentiation compared to wild-type mice; however, treatment of BMSCs from myostatin-deficient mice with recombinant myostatin did not attenuate the osteogenic differentiation of these cells. Loading of BMSCs in vitro increased the expression of osteogenic factors such as BMP-2 and IGF-1, but treatment of BMSCs with recombinant myostatin was found to decrease the expression of these factors. We investigated the effects of myostatin loss-of-function on the differentiation of BMSCs in vivo using hindlimb unloading (7-day tail suspension). Unloading caused a greater increase in marrow adipocyte number, and a greater decrease in osteoblast number, in myostatin-deficient mice than in normal mice. These data suggest that the increased osteogenic differentiation of BMSCs from mice lacking myostatin is load-dependent, and that myostatin may alter the mechanosensitivity of BMSCs by suppressing the expression of osteogenic factors during mechanical stimulation. Furthermore, although myostatin deficiency increases muscle mass and bone strength, it does not prevent muscle and bone catabolism with unloading.

Relative motion of a mobile bearing inlay after total knee arthroplasty--dynamic in vitro study.

OBJECTIVE: The purpose of this study was to measure the in vitro range of motion of a mobile bearing inlay knee prosthesis under dynamic isokinetic loading conditions. Additionally, the effect on the range of motion of rotational malalignment of the tibia baseplate was determined. DESIGN: Specimens with implanted knee prostheses were mounted onto a custom built knee simulator. 3-D inlay movement was measured by an ultrasonic tracking system. BACKGROUND: More recent knee prostheses include mobile bearing inlays type designs. These systems are intended to allow higher conformity of the tibiofemoral joint and thereby decrease contact stress without decreasing the knee's range of motion. METHODS: Dynamic testing in the knee simulator mimicked both the speed and resulting moment of a knee isokinetic extension test. The tibia baseplate was first implanted with no rotational malalignment, followed by sequential internal and external rotation of upto 15 degrees. RESULTS: Correctly aligned, the inlay center moved 3.5 mm (SD, 1.5 mm) posterior during extension. With the tibia baseplate externally rotated more than 10 degrees the movement pattern changed. CONCLUSION: At up to 10 degrees of rotational malalignment the primary motion pattern of the mobile bearing is maintained. However, beyond 10 degrees unintended motion may occur. RELEVANCE: These test results correlate to radiographic measurements of in vivo movements of mobile bearing inlays showing "paradoxical" movement of the mobile inlay compared to physiologic meniscal movement.

Technical note: biomechanical analysis of two absorbable fracture fixation pins after long-term canine implantation.

The design requirements for bioabsorbable fracture fixation devices for specific applications are as yet unknown. Therefore, a range of initial mechanical properties and degradation kinetics may provide developers with additional choices for the design of absorbable fracture fixation devices. This study evaluated the changes in push-out strength, polymer mechanical properties, and bone mechanical properties of self-reinforced poly(glycolide) (SR-PGA) and poly(ortho ester) (POE) fracture fixation pins implanted into the canine femoral canal for 18 months. Mechanical testing indicated that SR-PGA pins had degraded to a pasty consistency by 3 months, showing complete loss of all mechanical properties. Meanwhile, POE pins showed a simultaneous linear decrease in both compressive strength and stiffness to almost zero by the end of the study period, suggesting that these devices were undergoing surface erosion. However, changes in specimen diameter, which would support this mechanism, were not apparent. The decrease in polymer density after 12 months suggests that there was an increase in bulk erosion for POE devices. This was further supported by the observation of internal polymer resorption noticed in specimen cross-sections after 18 months. This observation appears to be related to the method of polymer processing; hot-compression molding of fine powdered polymer. The appearance of grain boundaries would provide a path for water to penetrate into the bulk polymer and cause autocatalysis in the interior of the implant.

Multiple muscle force simulation in axial rotation of the cervical spine.

OBJECTIVE: To produce axial rotation of the cervical spine in vitro by coordinated application of eight simulated muscle forces. DESIGN: Biomechanical testing of the cervical spine by controlled pneumatics. BACKGROUND: Some muscle simulation experiments have been performed in vitro in the lumbar spine but data generally are lacking for this testing mode in the cervical spine. Thus, physiological biomechanical behavior in this region remains poorly understood. METHODS: Six human donor cervical spines were loaded by a set of computer-controlled pneumatic cylinders representing pairs of trapezius, splenius and sternocleiodmastoid muscles, plus longus and splenius colli left. Muscle functions were derived from a previously-developed mathematical optimization model. Muscle forces generally were achievable within 2 N of the intended values provided by the model. RESULTS: Rotation of the head followed fairly closely that predicted by the model. The resulting force components to produce 37 degrees were dominated by axial compression of about--100 N and the resulting moments were similar in all planes at about 2 Nm. Coupled motions were larger than primary motions in some intersegmental behavior. CONCLUSIONS: Slow, physiologic axial rotation of the head may be simulated by a complex and representative series of controlled pneumatics. Controlled rotation results in a relatively high compressive force and occurs through fairly balanced and small moments. RELEVANCE: Experimental approaches in biomechanics are generally limited to one or two simplified muscle forces whose representation of in vivo loading conditions can only be presumed. Improvements in the application of pneumatic technology are a promising approach to more thoroughly duplicating the physiological loading environment.

Anatomy of the sheep spine and its comparison to the human spine.

BACKGROUND: The sheep spine is often used as a model for the human spine, although the degree to which these spines are anatomically comparable has yet to be categorically established. The purpose of this study was to investigate the characteristic anatomical dimensions of the sheep spine and to compare these with existing human data. METHODS: Five complete spines were measured to determine 21 dimensions from the pedicles, spinal canal, transverse and spinous processes, facets, endplates, and disc. RESULTS: The results showed that sheep and human vertebrae are most similar in the thoracic and lumbar regions, although they show substantial differences in certain dimensions. Morphological variations as a function of spine level typically were well matched in the two species. CONCLUSIONS: Sheep spine may be a useful model for experiments related to the gross structure of the thoracic or lumbar spine, with certain limitations for the cervical spine. A thorough database has been provided for deciding the appropriateness of using the sheep spine as a model for the human spine.

Load-displacement properties of the thoracolumbar calf spine: experimental results and comparison to known human data.

The availability of human cadaveric spine specimens for in vitro tests is limited and the risk of infection is now of vital concern. As an alternative or supplement, calf spines have been used as models for human spines, in particular to evaluate spinal implants. However, neither qualitative nor quantitative biomechanical data on calf spines are available for comparison with data on human specimens. The purpose of this study was to determine the fundamental biomechanical properties of calf spines and to compare them with existing data from human specimens. Range of motion, neutral zone, and stiffness properties of thoracolumbar calf spines (T6-L6) were determined under pure moment loading in flexion and extension, axial left/right rotation and right/left lateral bending. Biomechanical similarities were observed between the calf and reported human data, most notably in axial rotation and lateral bending. Range of motion in the lumbar spine in flexion and extension was somewhat less in the calf than that typically reported for the human, though still within the range. These results suggest that the calf spine can be considered on a limited basis as a model for the human spine in certain in vitro tests.

Biomechanical evaluation of the stability of thoracolumbar burst fractures.

STUDY DESIGN: The decision to treat thoracolumbar burst fractures in neurologically intact patients either surgically or nonoperatively depends largely on whether the fracture is clinically stable. This study evaluated the relative contributions of the anterior, middle, and posterior columns to spinal stability by way of in vitro experimentation and supplemental analysis of patients with nonoperatively treated burst fractures. METHODS: An L1 burst fracture model was used to evaluate the contribution of the three columns of the spine to resisting imposed flexion deforming forces. Six spines were tested to a gross bending flexion angle of 25 degrees. Changes in vertebral motion across the site of injury were measured and compared. In addition, a summary of our recent clinical experience with nonoperatively treated burst fractures is presented and correlated with the study's laboratory findings. RESULTS: T12-L2 motion measurements after vertebral and ligamentous disruption revealed a statistically significant increase in motion upon anterior and added posterior column compromise, but not for added middle column disruption. Review of the clinical series revealed that burst fractures with anterior and middle column compromise but an intact posterior column were stable and healed satisfactorily. CONCLUSIONS: The data suggest that the condition of the posterior column, not the middle column, is a better indicator of burst fracture stability. It is proposed that the classic burst fracture (anterior and middle column compromise) is a stable injury that, in the absence of neurologic deficit, can be managed nonoperatively.