TY - JOUR
T1 - Combined exposure to big endothelin-and mechanical loading in bovine sternal cores promotes osteogenesis
AU - Meyer, Luisa A.
AU - Johnson, Michael G.
AU - Cullen, Diane M.
AU - Vivanco, Juan F.
AU - Blank, Robert D.
AU - Ploeg, Heidi Lynn
AU - Smith, Everett L.
N1 - Publisher Copyright:
© 2016.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-(big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2 × 2 factorial trial of daily mechanical loading (-2000 με, 120 cycles daily, "jump" waveform) and big ET1 (25 ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23 days. The bone cores' response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (δEapp), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher's LSD test found no significant treatment effects on δEapp (= 0.25 and 0.51 for load and big ET1, respectively). The δEapp in the "no load + big ET1" (CE, 13 ± 12.2%, p = 0.56), "load + no big ET1" (LC, 17 ± 3.9%, p = 0.14) and "load + big ET1" (LE, 19 ± 4.2%, p = 0.13) treatment groups were not statistically different than the control group (CC, 3.3% ± 8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (= 0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (= 0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (= 0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (= 0.037, p = 0.055 respectively) and MAR (= 0.0040, p = 0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (= 0.019) and LC (= 0.074) than CC. The PGE2 levels were elevated at 8 days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15, 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses.
AB - Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-(big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2 × 2 factorial trial of daily mechanical loading (-2000 με, 120 cycles daily, "jump" waveform) and big ET1 (25 ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23 days. The bone cores' response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (δEapp), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher's LSD test found no significant treatment effects on δEapp (= 0.25 and 0.51 for load and big ET1, respectively). The δEapp in the "no load + big ET1" (CE, 13 ± 12.2%, p = 0.56), "load + no big ET1" (LC, 17 ± 3.9%, p = 0.14) and "load + big ET1" (LE, 19 ± 4.2%, p = 0.13) treatment groups were not statistically different than the control group (CC, 3.3% ± 8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (= 0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (= 0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (= 0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (= 0.037, p = 0.055 respectively) and MAR (= 0.0040, p = 0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (= 0.019) and LC (= 0.074) than CC. The PGE2 levels were elevated at 8 days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15, 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses.
KW - Bioreactor
KW - Endothelin
KW - Mechanical loading
KW - Osteogenesis
KW - Trabecular bone
UR - http://www.scopus.com/inward/record.url?scp=84957808991&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2016.02.001
DO - 10.1016/j.bone.2016.02.001
M3 - Article
C2 - 26855374
AN - SCOPUS:84957808991
SN - 8756-3282
VL - 85
SP - 115
EP - 122
JO - Bone
JF - Bone
ER -