Oral bone loss induced by mineral deficiency in a rat model: Effect of a synthetic bone mineral (SBM) preparation

Authors

Dindo Mijares, Anupama Kulkarni, Kanthi Lewis, Fang Yao, Qing Xi, Samar Tannous, Renata Dias, Racquel Z. LeGeros

Abstract

Osteoporosis affects the craniofacial and oral structures and has been associated with periodontal bone loss, tooth loss and reduced jaw bone mass. This study aimed to test the therapeutic efficacy of synthetic bone mineral (SBM) in minimizing alveolar bone loss induced by mineral deficiency in a rat model. SBM consists of a calcium carbonate apatite (similar to bone apatite) matrix incorporating magnesium, zinc, and fluoride ions. Thirty female Sprague Dawley rats (2 months old) were randomly distributed into 3 groups (10 rats per group): GA (control), on basic diet; GB, on mineral deficient (MD) diet; and GC, on MD + SBM. The rats were sacrificed after 3 months, the jawbones were isolated and the soft tissues removed. Bone density was determined using X-ray radiography (Faxitron); mandibular cortical width, panoramic mandibular index, and alveolar resorption degree (M/M ratio) using BioquantOsteo; and bone micro-architecture micro-computed tomography and scanning electron microscopy. Compared to control (GA), the rats on MD diet (GB) experienced significant mandibular bone loss while the rats on MD + SBM diet (GC) experienced significantly less bone loss compared to the GB group. SBM, administered orally, may have the potential as an osteoporosis therapeutic agent in minimizing or preventing alveolar bone loss induced by mineral deficiency.

Link to Article

http://dx.doi.org/10.1016/j.archoralbio.2012.02.021

Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1

Authors

Xiaolin Tu, Jianquan Chen, Joohyun Lim, Courtney M. Karner, Seung-Yon Lee, Julia Heisig, Cornelia Wiese, Kameswaran Surendran, Raphael Kopan, Manfred Gessler, Fanxin Long

Abstract

Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo.

Link to Article

http://dx.doi.org/10.1371/journal.pgen.1002577

Biofunctionalization of the implant surface with different concentrations of a synthetic peptide (P-15)

Authors

R. Lutz, C. Prechtl, J. Nonhoff, T. Weisel, C. J. Damien, K. A. Schlegel

Abstract

This study aimed at identifying the ideal concentration of a biofunctional surface coating of dental implants with a synthetic peptide (P-15). In a previous study, P-15 was shown to enhance osseointegration parameters. Implants (modified ANKYLOS® A8; FRIADENT Plus® surface) with five different concentrations (0–400 μg/ml) of a P-15 coating as well as uncoated controls were inserted in the frontal bone of 45 adult domestic pigs. The histomorphometric and microradiographic findings for the coated implants were compared to those for the uncoated ones after 7, 14, and 30 days. No significant differences were observed comparing the peri-implant bone density between the coated and uncoated implants The bone-to-implant contact, as the primary histological parameter for osseointegration, showed high rates for all surfaces investigated (between 73.3 ± 17.9% for the control and 81.9 ± 15.2% for P15 20 μg/ml after 30 days). No significant benefit on osseointegration of a biofunctional P-15 coating of dental implants could be displayed in the present study.

Link to Article

http://dx.doi.org/10.1111/j.1600-0501.2012.02455.x

Beta-tricalcium phosphate particles as a controlled release carrier of osteogenic proteins for bone tissue engineering

Authors

Junli Hu, Yaping Hou, Hyejin Park, Min Lee

Abstract

Beta-tricalcium phosphate (β-TCP) has been widely used as bone substitutes and delivery carriers of osteogenic proteins. However, low protein carrying capacity and agent burst release profiles of β-TCP limit their usage. This study investigates strategies to enhance protein carrying capacity of β-TCP particles with reduced initial burst by surface etching in citric acid solution or by creating apatite coatings with the simulate body fluid immersion approach. The release kinetics of protein from the modified β-TCP particles was investigated using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein. Although chemical etching treatments reduced the initial burst release of protein from the particles, a rapid burst release was observed with high protein dose. In contrast, the burst release of protein was significantly reduced by the apatite coating and a high protein dose was successfully delivered over a prolonged period from the apatite-coated particles. Protein release was further modulated by simultaneously delivering proteins from two different substrates: acid-etched and apatite-coated particles. The bioactivity of the protein was preserved during the loading procedure onto the particles. In addition, protein-loaded particles maintained biological activity in the lyophilized state over 4 weeks. These findings suggest that the protein carrying capacity of β-TCP can be modulated by surface modification, which has a potential for use as a protein carrier with controlled release.

Link to Article

http://dx.doi.org/10.1002/jbm.a.34115

Serum response factor regulates bone formation via IGF-1 and Runx2 signals

Authors

Jianfeng Chen, Kaiyu Yuan, Xia Mao, Joseph M Miano, Hui Wu, Yabing Chen

Abstract

Serum response factor (SRF) plays vital roles in numerous cellular processes; however, the physiological function of SRF in skeletal tissue remains unknown. In several organ systems, SRF regulates the expression of insulin-like growth factor-1 (IGF-1), which is crucial for normal development of mineralized skeleton and bone remodeling throughout life. Here we show that conditional deletion of SRF in osteoblasts by osteocalcin-Cre generated viable mice with normal body size and body weight. In comparison with normal siblings, osteoblast-specific SRF deficient adult mice exhibited a marked decrease in bone mineral density and bone formation rate. Deletion of SRF in primary mouse calvarial osteoblasts reduced cell differentiation and mineralization in vitro. This was accompanied by a decrease in IGF-1 expression and secretion. Addition of IGF-1 in the culture media enhanced osteoblast differentiation in control cells and partially restored the mineralization defect of SRF deficient cells, supporting an important role of SRF in regulating IGF-1 and IGF-1-mediated osteoblast differentiation. IGF-1-induced Akt activation was inhibited in SRF deficient calvarial cells, and enhanced in the SRF overexpressed cells. In addition, SRF deficiency decreased the transcriptional activity of Runx2, the key transcription factor for osteogenesis. Overexpression of SRF induced Runx2 transactivity in control cells, and restored Runx2 transactivity in the SRF deficient cells. Taken together, we conclude that SRF is important for IGF-1-induced osteoblast differentiation and mineralization, via regulating IGF-1 expression and Runx2 transactivity.

Link to Article

http://dx.doi.org/10.1002/jbmr.1607

A Novel Calcium Aluminate-Melatonin Scaffold Enhances Bone Regeneration Within A Calvarial Defect

Authors

William P. Clafshenkel, James L. Rutkowski, Rachelle N. Palchesko, Jared D. Romeo, Ken A. McGowan, Ellen S. Gawalt, Paula A. Witt-Enderby

Abstract

Over 500,000 bone graft or bio-implant procedures are performed annually in the United States. It has been reported that osseous autograft procurement may result in donor site complications and bio-implant allografts have been associated with disease transmission. Ceramic scaffolds are only osteoconductive, limiting their clinical use. The objective of this study was to create a bone filler substitute with regenerating properties similar to natural bone. Therefore, melatonin and platelet-rich plasma (PRP) were utilized for their known osteoinductive properties. It was hypothesized that melatonin and/or PRP would enhance the osteoinductive and osteoconductive properties of calcium aluminate (CA) scaffolds to promote bone regeneration in a model of calvarial defects. The biocompatibility of CA and CA-Mel scaffolds were tested in vitro and in vivo. Data show that CA-Mel scaffolds, in comparison to CA scaffolds, enhanced the adhesion, viability and proliferation of normal human osteoblasts (NHost) cells but not that of NIH 3T3 fibroblasts. Data also showed that human adult mesenchymal stem cells grown on CA or CA-Mel scaffolds showed a time-dependent induction into osteoblasts over 14 days revealed through scanning electron microscopy and by alkaline phosphatase analyses. Implantation of CA-Mel scaffolds into critical size calvarial defects in female, ovariectomized rats showed that the CA-Mel scaffolds were biocompatible, allowed for tissue infiltration and showed evidence of scaffold biodegradation by 3 and 6 months. Bone regeneration, assessed using fluorochrome labeling at 3 and 6 months, was greatest in animals implanted with the CA-Mel scaffold. Overall, results from this study show that CA-Mel scaffolds were osteoconductive and osteoinductive.

Link to Article

http://dx.doi.org/10.1111/j.1600-079X.2012.00989.x