title: Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF beta-release in response to cyclic strain.
abstract: Mechanical stimulation of bone tissue by physical activity stimulates bone formation in normal bone and may attenuate bone loss of osteoporotic patients. However, altered responsiveness of osteoblasts in osteoporotic bone to mechanical stimuli may contribute to osteoporotic bone involution. The purpose of the present study was to investigate whether osteoblasts from osteoporotic patients and normal donors show differences in proliferation and TGF beta production in responses to cyclic strain. Human osteoblasts isolated from collagenase-treated bone explants of 10 osteoporotic patients (average age 70 +/- 6 yr) and 8 normal donors (average age 54 +/- 10 yr) were plated into elastic rectangular silicone dishes. Subconfluent cultures were stimulated by cyclic strain (1%, 1 Hz) in electromechanical cell stretching apparatus at three consecutive days for each 30 min. The cultures were assayed for proliferation, alkaline phosphatase activity and TGF beta release in each three parallel cultures. In all experiments, osteoblasts grown in the same elastic dishes but without mechanical stimulation served as controls. Significant differences between stimulated cultures and unstimulated controls were determined by a paired two-tailed Wilcoxon test. In comparison to the unstimulated controls, osteoblasts from normal donors significantly increased proliferation (p = 0.025) and TGF beta secretion (p = 0.009) into the conditioned culture medium. In contrast, osteoblasts from osteoporotic donors failed to increase both proliferation (p > 0.05) and TGF beta release (p > 0.05) in response to cyclic strain. Alkaline phosphatase activity was not significantly affected (p > 0.05) in normal as well as osteoporotic bone derived osteoblasts. These findings suggest a different responsiveness to 1% cyclic strain of osteoblasts isolated from normal and osteoporotic bone that could be influenced by both the disease of osteoporosis and the higher average age of the osteoporotic patient group. While osteoblasts from osteoporotic donors failed to increase proliferation and TGF beta release under the chosen mechanical strain regimen that stimulated both parameters in normal osteoblasts, it is possible that some other strain regimen would provide more effective stimulation of osteoporotic cells.
authors.affiliation: Abteilung für Unfallchirurgische Forschung und Biomechanik, Universität Ulm, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Neidlinger-Wilke
authors.forename: I
authors.initials: I
authors.lastname: Stalla
authors.forename: L
authors.initials: L
authors.lastname: Claes
authors.forename: R
authors.initials: R
authors.lastname: Brand
authors.forename: I
authors.initials: I
authors.lastname: Hoellen
authors.forename: S
authors.initials: S
authors.lastname: Rübenacker
authors.forename: M
authors.initials: M
authors.lastname: Arand
authors.forename: L
authors.initials: L
authors.lastname: Kinzl
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D001696:Biomechanical Phenomena; D002455:Cell Division; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D010024:Osteoporosis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D000469:Alkaline Phosphatase