Mechanical deformation and glycosaminoglycan content changes in a rabbit annular puncture disc degeneration model.

STUDY DESIGN: Evaluation of degenerated intervertebral discs from a rabbit annular puncture model by using specialized magnetic resonance imaging (MRI) techniques, including displacement encoding with stimulated echoes and a fast-spin echo (DENSE-FSE) acquisition and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). OBJECTIVE: To evaluate a rabbit disc degeneration model by using various MRI techniques. To determine the displacements and strains, spin-lattice relaxation time (T1), and glycosaminoglycan (GAG) distribution of degenerated discs as compared to normal and adjacent level discs. SUMMARY OF BACKGROUND DATA: Annular puncture of the intervertebral disc produces disc degeneration in rabbits. DENSE-FSE has been previously demonstrated in articular cartilage for the measurement of soft tissue displacements and strains. MRI also can measure the T1 of tissue, and dGEMRIC can quantify GAG concentration in cartilage. METHODS.: In eight New Zealand white rabbits, the annulus fibrosis of a lumbar disc was punctured. After 4 weeks, the punctured and cranially adjacent motion segments were isolated for MRI and histology. MRI was used to estimate the disc volume and map T1. DENSE-FSE was used to determine displacements for the estimation of strains. dGEMRIC was then used to determine GAG distributions. RESULTS: Histology and standard MRI indicated degeneration in punctured discs. Disc volume increased significantly at 4 weeks after the puncture. Displacement of the nucleus pulposus was distinct from that of the annulus fibrosis in most untreated discs but not in punctured discs. T1 was significantly higher and GAG concentration significantly lower in punctured discs compared with untreated adjacent level discs. CONCLUSION: Noninvasive and quantitative MRI techniques can be used to evaluate the mechanical and biochemical changes that occur with animal models of disc degeneration. DENSE-FSE, dGEMRIC, and similar techniques have potential for evaluating the progression of disc degeneration and the efficacy of treatments.

Biomechanical comparison of double-row locking plates versus single- and double-row non-locking plates in a comminuted metacarpal fracture model.

PURPOSE: Open or unstable metacarpal fractures frequently require open reduction and internal fixation. Locking plate technology has improved fixation of unstable fractures in certain settings. In this study, we hypothesized that there would be a difference in strength of fixation using double-row locking plates compared with single- and double-row non-locking plates in comminuted metacarpal fractures. METHODS: We tested our hypothesis in a gap metacarpal fracture model simulating comminution using fourth-generation, biomechanical testing-grade composite sawbones. The metacarpals were divided into 6 groups of 15 bones each. Groups 1 and 4 were plated with a standard 6-hole, 2.3-mm plate in AO fashion. Groups 2 and 5 were plated with a 6-hole double-row 3-dimensional non-locking plate with bicortical screws aimed for convergence. Groups 3 and 6 were plated with a 6-hole double-row 3-dimensional locking plate with unicortical screws. The plated metacarpals were then tested to failure against cantilever apex dorsal bending (groups 1-3) and torsion (groups 4-6). RESULTS: The loads to failure in groups 1 to 3 were 198 +/- 18, 223 +/- 29, and 203 +/- 19 N, respectively. The torques to failure in groups 4 to 6 were 2,033 +/- 155, 3,190 +/- 235, and 3,161 +/- 268 N mm, respectively. Group 2 had the highest load to failure, whereas groups 5 and 6 shared the highest torques to failure (p < .05). Locking and non-locking double-row plates had equivalent bending and torsional stiffness, significantly higher than observed for the single-row non-locking plate. No other statistical differences were noted between groups. CONCLUSIONS: When subjected to the physiologically relevant forces of apex dorsal bending and torsion in a comminuted metacarpal fracture model, double-row 3-dimensional non-locking plates provided superior stability in bending and equivalent stability in torsion compared with double-row 3-dimensional locking plates, whereas single-row non-locking plates provided the least stability.

Comparison of metacarpal plating methods.

PURPOSE: Most metacarpal fractures are stable and can be treated with nonsurgical stabilization. However, some metacarpal fractures are treated with open reduction and internal fixation because of an open fracture, instability, or multiple fractures. Newer plate designs have emerged that allow a shorter plate and screw construct. We sought to determine the relative strength of 3 different methods of metacarpal plating for unstable fractures. METHODS: We tested our hypothesis in a transverse metacarpal fracture model using fourth-generation, biomechanical testing grade composite sawbones (Sawbones; Pacific Research Laboratories, Vashon, WA). The metacarpals were divided into 3 groups of 15 bones. Group 1 was plated with a standard 6-hole, 2.3-mm plate with 6 nonlocking bicortical screws in standard AO fashion. Group 2 was plated with a 6-hole, double-row, 3-dimensional (3D) plate with 3 nonlocking screws on either side of the fracture aiming for convergence of the screws. Group 3 was plated with a 2.4-mm plate using 6 nonlocking screws and standard AO technique. The metacarpals were then tested to failure in cantilever bending mode. RESULTS: All constructs broke through the bone. No plate failure or screw pullout was seen. Group 1 had a load to failure of 264 N +/- 14. Group 2 had a load to failure of 302 N +/- 17. Group 3 had a load to failure of 274 N +/- 20. The load to failure was highest in group 2 (3D plate). All differences were statistically significant. CONCLUSIONS: All 3 methods produced a strong construct. The load to failure was highest in group 2 (3D plate). Double-row plates with converging screws provide adequate or superior strength of fixation when compared with standard plate constructs.

Quantitative regional associations between remodeling, modeling, and osteocyte apoptosis and density in rabbit tibial midshafts.

Evidence suggests that osteocyte apoptosis is involved in the adaptive response of bone, although the specific role of osteocytes in the signaling mechanism is unknown. Here, we examined and correlated regional variability in indices of remodeling, modeling, osteocyte apoptosis, and osteocyte density in rabbit tibia midshafts. Histomorphometric analysis indicated that remodeling parameters (BMU activation frequency, osteon density, forming osteon density, and resorption cavity density) were lower in the cranial region compared to other quadrants. In addition, pericortical subregions displayed less remodeling relative to intracortical and endocortical ones. Modeling indices also demonstrated regional variability in that periosteal surfaces exhibited a greater extent of bone forming surface than endosteal ones across all anatomic quadrants. In contrast, endosteal surfaces demonstrated significantly greater surface mineral apposition rates compared to periosteal surfaces in caudal, medial, and lateral but not cranial quadrants. Using TUNEL analysis to detect osteocytes undergoing apoptosis, the density of apoptotic osteocytes was found to be lower in cranial quadrants relative to medial ones. In addition, the densities of osteocyte lacunae, empty lacunae, and total osteocytes were higher in lateral fields relative to caudal quadrants. There was a strong, statistically significant linear correlation between the remodeling indices and apoptotic osteocyte density, supporting the theory that osteocytes undergoing apoptosis produce signals that attract or direct bone remodeling. In contrast, the modeling parameters did not exhibit a correlation with apoptotic osteocytes, although there was a strong correlation between the modeling indices and the density of empty osteocyte lacunae, corroborating previous studies that have found that osteocytes inhibit bone formation. It was found that osteocyte density and osteocyte lacunar density did not significantly correlate with modeling or remodeling parameters, suggesting that cell viability should be examined in studies correlating bone turnover parameters with the functional role of osteocytes in bone adaptation.

Generation of interleukin-17 receptor-like protein (IL-17RL) in prostate by alternative splicing of RNA.

BACKGROUND: Interleukin-17 receptor-like protein (IL-17RL) expressed in prostate tissues changes with advanced cancers due to extensive alternative splicing, which affects the final protein. Predominant IL-17RL splice isoform variants have not been identified, hindering functional studies. METHODS: A cDNA library of IL-17RL transcripts was arrayed onto nylon membranes. Individual transcript exon structures were determined by successively probing membranes with exon-specific oligonucleotides. The most common variants were transiently over-expressed in 293T cells. RESULTS: We detected >90 different IL-17RL isoforms. Three most abundant isoforms account for approximately half the total transcripts; the full-length variant just over 11%. Surprisingly, most alternative splicing does not alter the reading frame of the full-length molecule; therefore, resulting proteins vary mostly in N-terminal domains. CONCLUSIONS: IL-17RL exists as multiple isoforms due to extensive alternative splicing. We identified the most abundant splices in prostate tissue and established a technique to investigate changes in RNA IL-17RL splicing that occur in advanced cancers.