Browsing by Author "Zelenski, Nicole A"

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Open Access
Altered trabecular bone structure and delayed cartilage degeneration in the knees of collagen VI null mice.
(PLoS One, 2012) Christensen, Susan E; Coles, Jeffrey M; Zelenski, Nicole A; Furman, Bridgette D; Leddy, Holly A; Zauscher, Stefan; Bonaldo, Paolo; Guilak, Farshid
Mutation or loss of collagen VI has been linked to a variety of musculoskeletal abnormalities, particularly muscular dystrophies, tissue ossification and/or fibrosis, and hip osteoarthritis. However, the role of collagen VI in bone and cartilage structure and function in the knee is unknown. In this study, we examined the role of collagen VI in the morphology and physical properties of bone and cartilage in the knee joint of Col6a1(-/-) mice by micro-computed tomography (microCT), histology, atomic force microscopy (AFM), and scanning microphotolysis (SCAMP). Col6a1(-/-) mice showed significant differences in trabecular bone structure, with lower bone volume, connectivity density, trabecular number, and trabecular thickness but higher structure model index and trabecular separation compared to Col6a1(+/+) mice. Subchondral bone thickness and mineral content increased significantly with age in Col6a1(+/+) mice, but not in Col6a1(-/-) mice. Col6a1(-/-) mice had lower cartilage degradation scores, but developed early, severe osteophytes compared to Col6a1(+/+) mice. In both groups, cartilage roughness increased with age, but neither the frictional coefficient nor compressive modulus of the cartilage changed with age or genotype, as measured by AFM. Cartilage diffusivity, measured via SCAMP, varied minimally with age or genotype. The absence of type VI collagen has profound effects on knee joint structure and morphometry, yet minimal influences on the physical properties of the cartilage. Together with previous studies showing accelerated hip osteoarthritis in Col6a1(-/-) mice, these findings suggest different roles for collagen VI at different sites in the body, consistent with clinical data.
Open Access
Salvage of Exposed Groin Vascular Grafts with Early Intervention Using Local Muscle Flaps.
(Plastic and reconstructive surgery. Global open, 2015-09-22) May, Brian L; Zelenski, Nicole A; Daluvoy, Sanjay V; Blanton, Matthew W; Shortell, Cynthia K; Erdmann, Detlev
BACKGROUND:Peripheral vascular surgery may be complicated by wound infection and potential graft exposure in the groin area. Muscle flap coverage of the graft has been promoted to address these wound complications. The authors present their findings regarding graft salvage rates and patient outcomes using local muscle flaps to address vascular graft complications of the groin. METHODS:Data were obtained by retrospective cohort study of patients who underwent a local muscle flap procedure by a single surgeon following vascular graft complication in the groin. RESULTS:Seventeen patients undergoing local muscle flap coverage of a vascular graft were reviewed. Six men and 9 women, 51-80 years old, were included in the study. Wound complications in the groin occurred anywhere from 3 days to 3.5 years following graft placement. Graft exposure was the most common presenting complication (14 of 17 patients). Muscle flap coverage occurred within 15 days of complication presentation in all patients (average, 6.4 days). Seven of the 15 patients experienced postoperative complications within 6 months of the procedure, most commonly wound dehiscence. However, analysis demonstrated that vascular grafts were successfully salvaged in 10 of the 17 patients (59%) over the course of follow-up (range, 104-1748 days). Average time to muscle flap coverage was 4.2 days in patients who retained the graft and 9.6 days in patients who ultimately lost their vascular graft. CONCLUSION:The authors demonstrate improved vascular graft salvage rate when local muscle flap procedure is performed early after initial wound complication presentation.
Open Access
Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.
(Proc Natl Acad Sci U S A, 2014-11-25) Lee, Whasil; Leddy, Holly A; Chen, Yong; Lee, Suk Hee; Zelenski, Nicole A; McNulty, Amy L; Wu, Jason; Beicker, Kellie N; Coles, Jeffrey; Zauscher, Stefan; Grandl, Jörg; Sachs, Frederick; Guilak, Farshid; Liedtke, Wolfgang B
Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca(2+) signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca(2+) transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1- or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains.