Osteoblast-like cells and fluid flow: cytoskeleton-dependent shear sensitivity.
The cytoskeleton is thought to play a central role in cellular mechanotransduction. However, the specific mechanisms operative in bone cells have not yet been clearly elucidated. Isolating the roles of the specific cytoskeletal elements could ultimately aid in development of treatments for conditions related to the mechanoresponsiveness of bone (e.g. osteoporosis, space flight). Using an osteoblast-like cell line, the minimum doses of nocodazole (microtubules) and cytochalasin D (actin filaments) that would partially disrupt the cytoskeleton while leaving some elements intact were determined. Cultures were exposed to fluid flow shear, and loaded in the presence or absence of inhibitory drugs at the previously established doses. In untreated cultures, shear stress was associated with significant increases in mRNA levels for collagen I and matrix metalloproteinases 1 and 3. These increases were maintained in cytochalasin D-treated cultures, but were almost completely abrogated by nocodazole treatment. These results suggest that some mechanotransduction pathways related to bone matrix metabolism are primarily dependent on the microtubule network.
Myers
Kenneth A
KA
McCaig Institute for Bone and Joint Health, University of Calgary, Rm 431 Heritage Medical Research Building, 3330 Hospital Dr. NW, Calgary, Alta., Canada T2N 4N1.
Rattner
Jerome B
JB
Shrive
Nigel G
NG
Hart
David A
DA
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D044085:Microfluidics; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D013314:Stress, Mechanical
D024042:Collagen Type I; D015638:Cytochalasin D; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D015739:Nocodazole