PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 21Citation - Scopus: 22Daily Application of Low Magnitude Mechanical Stimulus Inhibits the Growth of Mda-Mb Breast Cancer Cells in Vitro(BioMed Central Ltd., 2014) Ölçüm, Melis; Özçivici, EnginIntroduction: Mechanical loads can regulate cell proliferation and differentiation at various stages of development and homeostasis. However, the extension of this regulatory effect of mechanical loads on cancer cells is largely unknown. Increased physical compliance is one of the key features of cancer cells, which may hamper the transmission of mechanical loads to these cells within tumor microenvironment. Here we tested whether brief daily application of an external low magnitude mechanical stimulus (LMMS), would impede the growth of MDA-MB-231 aggressive type breast cancer cells in vitro for 3 wks of growth. Methods: The signal was applied in oscillatory form at 90 Hz and 0.15 g, a regimen that would induce mechanical loads on MDA-MB-231 cells via inertial properties of cells rather than matrix deformations. Experimental cells were exposed to LMMS 15 min/day, 5 days/week in ambient conditions while control cells were sham loaded. Cell proliferation, viability, cycle, apoptosis, morphology and migration were tested via Trypan Blue dye exclusion, MTT, PI, Annexin V, Calcein-AM and phalloidin stains and scratch wound assays. Results: Compared to sham controls, daily application of LMMS reduced the number and viability of cancerous MDA-MB-231 cells significantly after first week in the culture, while non-cancerous MCF10A cells were found to be unaffected. Flow cytomety analyses suggested that the observed decrease for the cancer cells in the LMMS group was due to a cell cycle arrest rather than apoptosis. LMMS further reduced cancer cell circularity and increased cytoskeletal actin in MDA-MB-231 cells. Conclusion: Combined, results suggest that direct application of mechanical loads negatively regulate the proliferation of aggressive type cancer cells. If confirmed, this non-invasive approach may be integrated to the efforts for the prevention and/or treatment of cancer.Article Citation - WoS: 25Citation - Scopus: 27Trabecular Bone Recovers From Mechanical Unloading Primarily by Restoring Its Mechanical Function Rather Than Its Morphology(Elsevier Ltd., 2014) Özçivici, Engin; Judex, StefanUpon returning to normal ambulatory activities, the recovery of trabecular bone lost during unloading is limited. Here, using a mouse population that displayed a large range of skeletal susceptibility to unloading and reambulation, we tested the impact of changes in trabecular bone morphology during unloading and reambulation on its simulated mechanical properties. Female adult mice from a double cross of BALB/cByJ and C3H/HeJ strains (n = 352) underwent 3. wk of hindlimb unloading followed by 3. wk of reambulation. Normally ambulating mice served as controls (n = 30). As quantified longitudinally by in vivo μCT, unloading led to an average loss of 43% of trabecular bone volume fraction (BV/TV) in the distal femur. Finite element models of the μCT tomographies showed that deterioration of the trabecular structure raised trabecular peak Von-Mises (PVM) stresses on average by 27%, indicating a significant increase in the risk of mechanical failure compared to baseline. Further, skewness of the Von-Mises stress distributions (SVM) increased by 104% with unloading, indicating that the trabecular structure became inefficient in resisting the applied load. During reambulation, bone of experimental mice recovered on average only 10% of its lost BV/TV. Even though the addition of trabecular tissue was small during reambulation, PVM and SVM as indicators of risk of mechanical failure decreased by 56% and 57%, respectively. Large individual differences in the response of trabecular bone, together with a large sample size, facilitated stratification of experimental mice based on the level of recovery. As a fraction of all mice, 66% of the population showed some degree of recovery in BV/TV while in 89% and 87% of all mice, PVM and SVM decreased during reambulation, respectively. At the end of the reambulation phase, only 8% of the population recovered half of the unloading induced losses in BV/TV while 50% and 49% of the population recovered half of the unloading induced deterioration in PVM and SVM, respectively. The association between morphological and mechanical variables was strong at baseline but progressively decreased during the unloading and reambulation cycles. The preferential recovery of trabecular micromechanical properties over bone volume fraction emphasizes that mechanical demand during reambulation does not, at least initially, seek to restore bone's morphology but its mechanical integrity.Article Citation - WoS: 8Citation - Scopus: 9Quantitative Trait Loci That Modulate Trabecular Bone's Risk of Failure During Unloading and Reloading(Elsevier Ltd., 2014) Özçivici, Engin; Zhang, Weidong; Donahue, Leah Rae; Judex, StefanGenetic makeup of an individual is a strong determinant of the morphologic and mechanical properties of bone. Here, in an effort to identify quantitative trait loci (QTLs) for changes in the simulated mechanical parameters of trabecular bone during altered mechanical demand, we subjected 352. second generation female adult (16. weeks old) BALBxC3H mice to 3. weeks of hindlimb unloading followed by 3. weeks of reambulation. Longitudinal in vivo microcomputed tomography (μCT) scans tracked trabecular changes in the distal femur. Tomographies were directly translated into finite element (FE) models and subjected to a uniaxial compression test. Apparent trabecular stiffness and components of the Von Mises (VM) stress distributions were computed for the distal metaphysis and associated with QTLs. At baseline, five QTLs explained 20% of the variation in trabecular peak stresses across the mouse population. During unloading, three QTLs accounted for 14% of the variability in peak stresses. During reambulation, one QTL accounted for 5% of the variability in peak stresses. QTLs were also identified for mechanically induced changes in stiffness, median stress values and skewness of stress distributions. There was little overlap between QTLs identified for baseline and QTLs for longitudinal changes in mechanical properties, suggesting that distinct genes may be responsible for the mechanical response of trabecular bone. Unloading related QTLs were also different from reambulation related QTLs. Further, QTLs identified here for mechanical properties differed from previously identified QTLs for trabecular morphology, perhaps revealing novel gene targets for reducing fracture risk in individuals exposed to unloading and for maximizing the recovery of trabecular bone's mechanical properties during reambulation.