Mechanical strain threshold for lamellar bone formation

The purpose of the present study was to observe the response and changes of cranial suture to the distraction forces in growing goats and to examine the expression patterns of TGF-β and BMP during suture distraction.Twenty growing goats were divided into three groups: control (n=4), experimental (n=12), and sham (n=4). A pure titanium distractor was placed in the coronal suture in both the sham and experimental groups. After healing, the distractor was activated for distraction of the coronal suture at a rate of 0.5 mm/day for 8 days in the experimental group. Three animals were killed respectively, at 0，2，4 and 8 weeks after completion of suture distraction. No force was applied in the sham group. X- Ray examination was taken and the coronal suture samples were harvested and processed for histological analysis and scanning electron microscopic analysis and immunohistochemistry of TGF-β and BMP. The coronal sutures of experimental group were separated successfully. Signs of intramembranous bone formation and remodeling were found in the distracted suture，and the sutural structure almost return to its normal state at 8 weeks after end of distraction. At 0 and 2 weeks after completion of suture distraction, the collagen fiber bundles were strengthened and aligned in the direction of the distracted forces. Strong expression of BMP and TGF-β were detected in the fibroblast-like cells and the active osteoblasts. At 4 weeks after suture distraction, signs of intramembranous ossification were found in the edge areas of the distracted suture, and the positive staining of BMP and TGF-β was still noted in the osteoblasts around the newly formed bone trabeculae. This study suggests that cranial suture expansion can be achieved in growing animal by distraction osteogenesis. Mechanical strain resulted from distractor can induce the adaptive remodeling in the cranial suture of growing goats. It also suggests BMP and TGF-β may play very important roles in the process of bone formation and remodeling during suture distraction osteogenesis.

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Morphologie stages in lamellar bone formation stimulated by a potent mechanical stimulus

Journal of Bone and Mineral Research ◽

10.1002/jbmr.5650100321 ◽

2009 ◽

Vol 10 (3) ◽

pp. 488-495 ◽

Cited By ~ 72

Author(s):

Clinton T. Rubin ◽

Ted S. Gross ◽

Kenneth J. McLeod ◽

Steven D. Bain

Keyword(s):

Bone Formation ◽

Mechanical Stimulus ◽

Lamellar Bone

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Differential Gene Expression from Microarray Analysis Distinguishes Woven and Lamellar Bone Formation in the Rat Ulna following Mechanical Loading

PLoS ONE ◽

10.1371/journal.pone.0029328 ◽

2011 ◽

Vol 6 (12) ◽

pp. e29328 ◽

Cited By ~ 25

Author(s):

Jennifer A. McKenzie ◽

Elise C. Bixby ◽

Matthew J. Silva

Keyword(s):

Gene Expression ◽

Bone Formation ◽

Differential Gene Expression ◽

Mechanical Loading ◽

Microarray Analysis ◽

Lamellar Bone ◽

Differential Gene

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In vivo lamellar bone formation in fibre coated MgCHA–PCL-composite scaffolds

Journal of Materials Science Materials in Medicine ◽

10.1007/s10856-011-4489-y ◽

2011 ◽

Vol 23 (1) ◽

pp. 117-128 ◽

Cited By ~ 13

Author(s):

Silvia Scaglione ◽

Vincenzo Guarino ◽

Monica Sandri ◽

Anna Tampieri ◽

Luigi Ambrosio ◽

...

Keyword(s):

Bone Formation ◽

Lamellar Bone ◽

Composite Scaffolds

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Parathyroid Hormone (1-34) Counteracts the Suppression of Interleukin-11 Expression by Glucocorticoid in Murine Osteoblasts: A Possible Mechanism for Stimulating Osteoblast Differentiation Against Glucocorticoid Excess

Endocrinology ◽

10.1210/en.2013-1915 ◽

2013 ◽

Vol 154 (3) ◽

pp. 1156-1167 ◽

Cited By ~ 7

Author(s):

Rika Kuriwaka-Kido ◽

Shinsuke Kido ◽

Yuka Miyatani ◽

Yuji Ito ◽

Takeshi Kondo ◽

...

Keyword(s):

Bone Formation ◽

Gene Transcription ◽

Osteoblast Differentiation ◽

Mechanical Strain ◽

Dependent Manner ◽

Rapid Induction ◽

Kinase C ◽

High Doses ◽

Interfering Rna ◽

Dose Dependent

Abstract Glucocorticoid (GC) excess causes a rapid loss of bone with a reduction in bone formation. Intermittent PTH (1-34) administration stimulates bone formation and counteracts the inhibition of bone formation by GC excess. We have previously demonstrated that mechanical strain enhances interleukin (IL)-11 gene transcription by a rapid induction of ΔFosB expression and protein kinase C (PKC)-δ-mediated phosphorylation of phosphorylated mothers against decapentaplegic (Smad)-1. Because IL-11 suppresses the expression of dickkopf-1 and -2 and stimulates Wnt signaling, IL-11 appears to mediate at least a part of the effect of mechanical strain on osteoblast differentiation and bone formation. The present study was undertaken to examine the effect of PTH(1-34) and GCs on IL-11 expression in murine primary osteoblasts (mPOBs). PTH(1-34) treatment of mPOBs enhanced IL-11 expression in a time- and dose-dependent manner. PTH(1-34) also stimulated ΔFosB expression and Smad1 phosphorylation, which cooperatively stimulated IL-11 gene transcription. PTH(1-34)-induced Smad1 phosphorylation was mediated via PKCδ and was abrogated in mPOBs from PKCδ knockout mice. Dexamethasone suppressed IL-11 gene transcription enhanced by PTH(1-34) without affecting ΔFosB expression or Smad1 phosphorylation, and dexamethasone-GC receptor complex was bound to JunD, which forms heterodimers with ΔFosB. High doses of PTH(1-34) counteracted the effect of dexamethasone on apoptosis of mPOBs, which was blunted by neutralizing anti-IL-11 antibody or IL-11 small interfering RNA. These results demonstrate that PTH(1-34) and GCs interact to regulate IL-11 expression in parallel with osteoblast differentiation and apoptosis and suggest that PTH(1-34) and dexamethasone may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression.

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Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing

Journal of Applied Physiology ◽

10.1152/japplphysiol.00957.2013 ◽

2014 ◽

Vol 116 (4) ◽

pp. 416-424 ◽

Cited By ~ 7

Author(s):

Ryan E. Tomlinson ◽

Kooresh I. Shoghi ◽

Matthew J. Silva

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Bone Formation ◽

Mechanical Loading ◽

Stress Fracture ◽

Flow Rate ◽

Vascular Function ◽

Blood Flow Rate ◽

Lamellar Bone ◽

Woven Bone

Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF),15O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas18F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF),15O water and18F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected.

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