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Inorganic polyphosphate (poly(P)) has recently been found to play an important role in bone formation. In this study, we found that tartrate-resistant acid phosphatase (TRAP), which is abundantly expressed in osteoclasts, has polyphosphatase activity that degrades poly(P) and yields Pi as well as shorter poly(P) chains. Since the TRAP protein that coprecipitated with anti-TRAP monoclonal antibodies exhibited both polyphosphatase and the original phosphatase activity, poly(P) degradation activity is dependent on TRAP and not on other contaminating enzymes. The ferrous chelator α, α'-bipyridyl, which inhibits the TRAP-mediated production of reactive oxygen species (ROS), had no effect on such poly(P) degradation, suggesting that the degradation is not dependent on ROS. In addition, shorter chain length poly(P) molecules were better substrates than longer chains for TRAP, and poly(P) inhibited the phosphatase activity of TRAP depending on its chain length. The IC50 of poly(P) against the original phosphatase activity of TRAP was 9.8 µM with an average chain length more than 300 phosphate residues, whereas the IC50 of poly(P) with a shorter average chain length of 15 phosphate residues was 8.3 mM. Finally, the pit formation activity of cultured rat osteoclasts differentiated by RANKL and M-CSF were markedly inhibited by poly(P), while no obvious decrease in cell number or differentiation efficiency was observed for poly(P). In particular, the inhibition of pit formation by long chain poly(P) with 300 phosphate residues was stronger than that of shorter chain poly(P). Thus, poly(P) may play an important regulatory role in osteoclastic bone resorption by inhibiting TRAP activity, which is dependent on its chain length.

In response to infection, macrophages produce a series of inflammatory mediators, including nitric oxide (NO), to eliminate pathogens. The production of these molecules is tightly regulated via various mechanisms, as excessive responses are often detrimental to host tissues. Here, we report that inorganic polyphosphate [poly(P)], a linear polymer of orthophosphate ubiquitously found in mammalian cells, suppresses inducible nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, in mouse peritoneal macrophages. Poly(P) with longer chains is more potent than those with shorter chains in suppressing LPS-induced iNOS expression. In addition, poly(P) decreased LPS-induced NO release. Moreover, poly(P) suppressed iNOS mRNA expression induced by LPS stimulation, thereby indicating that poly(P) reduces LPS-induced iNOS expression by down-regulation at the mRNA level. In contrast, poly(P) did not affect the LPS-induced release of TNF, another inflammatory mediator. Poly(P) may serve as a regulatory factor of innate immunity by modulating iNOS expression in macrophages.

OBJECTIVE: The aim of this study was to evaluate whether increased crown-to-implant (C/I) ratio influences implant stability or not under proper healthy control of peri-implant mucosa. The hypothesis of this study is that implant stability can be maintained despite High C/I, under appropriate plaque control. MATERIALS AND METHODS: Five male Beagle-Labrador hybrid dogs (2 years old) were used. Their bilateral mandibular premolar extraction was performed. After allowing 12 weeks for bone healing, 3 types of vertical marginal bone loss were simultaneously prepared randomly. Then, 30 titanium implants were placed in the edentulous areas and defined as High C/I, Mid C/I and Low C/I groups. This time point was designated as the baseline (0 Week). Twelve weeks after implant placement, metal superstructures were cemented to the implants and an occlusal plate was set at the opposite side. At the same time, Calcein green was injected for remodeling evaluation. Implants were loaded by feeding the dogs a hard pellet diet. Tooth brushing was performed 5 days per week during the study to maintain healthy peri-implant mucosa. Twenty-four weeks following implant placement, the interface structure was evaluated clinically, radiologically, and histologically. RESULT: Implant stability quotient (ISQ) increased with time in all 3 groups, without any significant correlation with the C/I value (p >0.05). Moreover, mean marginal bone loss adjacent around implants in all 3 groups ranged between 0.11 and 0.19 mm, with no significant difference (p >0.05). Many fluorescence-labeled bones are shown in the High C/I group. It is considered that high remodeling activity prevent marginal bone loss in the High C/I group and this may provide favorable implant stability under proper plaque control. CONCLUSION: These findings suggest that increased C/I may not be a risk factor for implant failure if the peri-implant mucosa is kept healthy, as was the case in this animal model.

BACKGROUND: Dental implant has been successfully used to replace missing teeth. However, in some clinical situations, implant placement may be difficult because of a large bone defect. We designed novel complex biomaterial to simultaneously restore bone and place implant. This complex was incorporated implant into interconnected porous calcium hydroxyapatite (IP-CHA). We then tested this Implant/IP-CHA complex and evaluated its effect on subsequent bone regeneration and implant stability in vivo. METHODOLOGY/PRINCIPAL FINDINGS: A cylinder-type IP-CHA was used in this study. After forming inside of the cylinder, an implant was placed inside to fabricate the Implant/IP-CHA complex. This complex was then placed into the prepared bone socket in the femur of four beagle-Labrador hybrid dogs. As a control, implants were placed directly into the femur without any bone substrate. Bone sockets were allowed to heal for 2, 3 and 6 months and implant stability quotients (ISQ) were measured. Finally, tissue blocks containing the Implant/IP-CHA complexes were harvested. Specimens were processed for histology and stained with toluidine blue and bone implant contact (BIC) was measured. The ISQs of complex groups was 77.8±2.9 in the 6-month, 72.0±5.7 in the 3-month and 47.4±11.0 in the 2-month. There was no significant difference between the 3- or 6-month complex groups and implant control groups. In the 2-month group, connective tissue, including capillary angiogenesis, was predominant around the implants, although newly formed bone could also be observed. While, in the 3 and 6-month groups, newly formed bone could be seen in contact to most of the implant surface. The BICs of complex groups was 2.18±3.77 in the 2-month, 44.03±29.58 in the 3-month, and 51.23±8.25 in the 6-month. Significant difference was detected between the 2 and 6-month. CONCLUSIONS/SIGNIFICANCE: Within the results of this study, the IP-CHA/implant complex might be able to achieve both bone reconstruction and implant stability.