Improved Trabecular Bone Structure of 20-Month-Old Male Spontaneously Hypertensive Rats

Authors

Tzu-Cheng Lee, Andrew J. Burghardt, Wei Yao, Nancy E. Lane, Sharmila Majumdar, Grant T. Gullberg, Youngho Seo

Abstract

A few clinical studies have reported that elderly male participants with hypertensive disease frequently have higher bone mineral density (BMD) than the normotensive participants at several skeletal sites. The detailed mechanism is still unknown; therefore, a study of bone structure and density using the hypertensive animal models could be informative. We used micro-computed tomography to quantitatively evaluate the tibial and 3rd lumbar vertebral bones in the 20-month-old male spontaneous hypertensive rat (SHR). The BMD, volume fraction, and the microarchitecture changes of the SHR were compared to those of same-age normotensive controls (Wistar-Kyoto rat, WKY). We found that in the very old (20 month) male rats, the trabecular bone fraction and microstructure were higher than those in the same-age normotensive controls. The observation of the association of hypertension with BMD and bone strength in hypertensive rats warrants further investigations of bone mass and strength in elderly males with hypertension.

Link To Article

http://dx.doi.org/10.1007/s00223-014-9893-0

Bone formation in peri-implant defects grafted with microparticles: a pilot animal experimental study

Authors

Tobias Moest, Franz Koehler, Christopher Prechtl, Christian Schmitt, Georg Watzek and Karl Andreas Schlegel

Abstract

Aim This study aimed to evaluate the healing of peri-implant defects grafted with microparticles (MPs).

Material and Methods Six domestic pigs received nine standardized defects at the calvaria, and an implant was inserted in the middle of each defect. The space between the implant and lateral bone portion was filled with MP pellets (n = 18) or MP supernatant (n = 18) or left unfilled (n = 18). After 14 and 28 days, three animals were sacrificed and specimens removed for further processing. Samples were microradiographically and histologically analysed. In addition, we immunohistochemically stained for anti-vWF as a marker of angiogenesis.

Results In the case of bone regeneration and vessel formation, the null hypothesis can be partially rejected. After 14 and 28 days, no significant difference was observed within groups regarding de novo bone formation, bone density and osseointegration. However, superior vessel formation was found at both time points.

Conclusion Microparticles represent a promising treatment option to accelerate peri-implant vessel formation. Further studies are needed to investigate the regenerative properties of MPs more precisely.

Link To Article

http://dx.doi.org/10.1111/jcpe.12295

N-cadherin Restrains PTH Activation of Lrp6/β-catenin Signaling and Osteoanabolic Action

Authors

Leila Revollo, Jacqueline Kading, Sung Yeop Jeong, Jiemin Li, Valerie Salazar, Gabriel Mbalaviele and Roberto Civitell

Abstract

Interaction between parathyroid hormone/parathyroid hormone-related peptide receptor 1 (PTHR1) and low density lipoprotein receptor-related protein 6 (Lrp6) is important for parathyroid hormone (PTH) signaling and anabolic action. Since N-cadherin has been shown to negatively regulate canonical Wnt/β-catenin signaling, we asked whether N-cadherin alters PTH signaling and stimulation of bone formation. Ablation of the N-cadherin gene (Cdh2) in primary osteogenic lineage cells resulted in increased Lrp6/PTHR1 interaction in response to PTH1-34, associated with enhanced PTH-induced PKA signaling and PKA-dependent β-catenin C-terminus phosphorylation, which promotes β-catenin transcriptional activity. β-catenin C-terminus phosphorylation was abolished by Lrp6 knockdown. Accordingly, PTH1-34 stimulation of Tcf/Lef target genes, Lef1 and Axin2, was also significantly enhanced in Cdh2 deficient cells. This enhanced responsiveness to PTH extends to the osteo-anabolic effect of PTH, as mice with a conditional Cdh2 deletion in Osx+ cells treated with intermittent doses of PTH1-34 exhibited significantly larger gains in trabecular bone mass relative to control mice, the result of accentuated osteoblast activity. Therefore, N-cadherin modulates Lrp6/PTHR1 interaction, restraining the intensity of PTH-induced β-catenin signaling, and ultimately influencing bone formation in response to intermittent PTH administration.

Link To Article

http://dx.doi.org/10.1002/jbmr.2323

Comparative study of the osseous healing process following three different techniques of bone augmentation in the mandible: an experimental study

Authors

M.E. Benlidayi, A. Gaggl, H. Buerger, O.E. Kahraman, L. Sencar, C. Brandtner, M. Kurkcu, S. Polat, F. Borumandi

Abstract

The aim of this study was to evaluate the osseointegration of three different bone grafting techniques. Forty-eight mature New Zealand rabbits were divided randomly into three groups of 16 each. Horizontal augmentation was performed on the corpus of the mandible using three different techniques: free bone graft (FBG), free periosteal bone graft (PBG), pedicled bone flap (BF). The animals were sacrificed at postoperative weeks 1, 3, or 8. Specimens were decalcified for histological examination, and histomorphometric measurements were performed. The histological evaluation demonstrated bony fusion between the grafts and the augmented mandibular bone after 8 weeks in all groups. At week 8, the bone volume was significantly greater in the BF group than in the FBG (P<0.001) and PBG (P=0.001) groups, and also the trabecular thickness was significantly greater than in the FBG (P=0.015) and PBG (P=0.015) groups. Trabecular separation was significantly lower in the BF group than in the FBG group at week 8 (P=0.015). BF demonstrated greater osseous healing capacity compared to FBG and PBG. The preserved vascularization in BF improves the bone quality in mandibular bone augmentations.

Link To Article

http://dx.doi.org/10.1016/j.ijom.2014.07.004

Effect of isolated hyperglycemia on native mechanical and biologic shoulder joint properties in a rat model

Authors

Stephen J. Thomas, Joseph J. Sarver, Sarah M. Yannascoli, Jennica J. Tucker, John D. Kelly IV, Rexford S. Ahima, Mary F. Barbe and Louis J. Soslowsky

Abstract

Recently, diabetes has been linked to rotator cuff disease and adhesive capsulitis, conditions with increased stiffness and inflammation. Unfortunately, limited research exists examining how hyperglycemia affects the native shoulder (tendon and capsule) properties. Therefore, the objectives of this study were to compare shoulder joint mechanics, tendon properties (mechanics and immunohistochemistry), and capsule of healthy control and hyperglycemic rats 8 weeks following induction of hyperglycemia with a submaximal dose of streptozotocin (STZ). Eighteen rats were injected with STZ to induce hyperglycemia or citrate buffer (control) and underwent normal cage activity for 8 weeks. Passive joint mechanics demonstrated significantly less external rotation in the hyperglycemic group compared to controls, with no other group differences. Tendon mechanical properties (stiffness and modulus) were not significantly different between groups at both the insertion site and mid-substance. Immunohistochemistry staining of the tendon and capsule demonstrated significantly increased interleukin 1-beta (IL1-β) and advanced glycated end-products (AGE) staining localized to the insertion and mid-substance of the tendon but not the capsule. In addition, tumor necrosis factor alpha (TNF-α) staining was significantly increased in the superior capsule but not the supraspinatus tendon. This study demonstrates that isolated hypergylcemia does not diminish shoulder mechanical properties but does induce a chronic inflammatory response.

Link To Article

http://dx.doi.org/10.1002/jor.22695

Loss of Runx2 in Committed Osteoblasts Impairs Postnatal Skeletogenesis

Authors

Mitra D. Adhami BS, Harunur Rashid MSc, Haiyan Chen PhD, John C. Clarke BS, Yang Yang MD and Amjad Javed PhD

Abstract

The Runx2 transcription factor is critical for commitment to the osteoblast lineage. However, its role in committed osteoblasts and its functions during postnatal skeletogenesis remain unclear. We established a Runx2-floxed line with insertion of loxP sites around exon 8 of the Runx2 gene. Runx2 protein lacking the region encoded by exon 8 is imported into the nucleus and binds target DNA, but exhibits diminished transcriptional activity. We specifically deleted the Runx2 gene in committed osteoblasts using 2.3kb col1a-Cre transgenic mice. Surprisingly, the homozygous Runx2 mutant mice were born alive. The Runx2 heterozygous and homozygous null were grossly indistinguishable from wild-type littermates at birth. Runx2 deficiency did not alter proliferative capacity of osteoblasts during embryonic development (E18). Chondrocyte differentiation and cartilage growth in mutants was similar to wild-type mice from birth to 3 months of age. Analysis of the embryonic skeleton revealed poor calcification in homozygous mutants, which was more evident in bones formed by intramembranous ossification. Runx2 mutants showed progressive retardation in postnatal growth and exhibited significantly low bone mass by 1 month of age. Decreased bone formation was associated with decreased gene expression of osteoblast markers and impaired collagen assembly in the extracellular matrix. Consequently, Runx2 mutant bones exhibited decreased stiffness and structural integrity. By 3 months of age, bone acquisition in mutant mice was roughly half that of wild-type littermates. In addition to impaired osteoblast function, mutant mice showed markedly decreased osteoclast number and postnatal bone resorption. Taken together, functional deficiency of Runx2 in osteoblasts does not result in failed embryonic skeletogenesis, but disrupts postnatal bone formation.

Link To Article

http://dx.doi.org/10.1002/jbmr.2321