scholarly journals Carbonate Apatite Containing Statin Enhances Bone Formation in Healing Incisal Extraction Sockets in Rats

Materials ◽  
2018 ◽  
Vol 11 (7) ◽  
pp. 1201 ◽  
Author(s):  
Yunia Rakhmatia ◽  
Yasunori Ayukawa ◽  
Akihiro Furuhashi ◽  
Kiyoshi Koyano
Keyword(s):  
Bone Formation ◽  
Tooth Extraction ◽  
Alveolar Bone ◽  
Vertical Plane ◽  
Precipitation Reaction ◽  
Carbonate Apatite ◽  
Mixed Solution ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Trabecular Thickness

The purpose of this study was to evaluate the feasibility of using apatite blocks fabricated by a dissolution–precipitation reaction of preset gypsum, with or without statin, to enhance bone formation during socket healing after tooth extraction. Preset gypsum blocks were immersed in a Na3PO4 aqueous solution to make hydroxyapatite (HA) low crystalline and HA containing statin (HAFS), or in a mixed solution of Na2HPO4 and NaHCO3 to make carbonate apatite (CO) and CO containing statin (COFS). The right mandibular incisors of four-week-old male Wistar rats were extracted and the sockets were filled with one of the bone substitutes or left untreated as a control (C). The animals were sacrificed at two and four weeks. Areas in the healing socket were evaluated by micro-computed tomography (micro-CT) and histological analyses. The bone volume, trabecular thickness, and trabecular separation were greatest in the COFS group, followed by the CO, HAFS, HA, and C groups. The bone mineral density of the COFS group was greater than that of the other groups when evaluated in the vertical plane. The results of this study suggest that COFS not only allowed, but also promoted, bone healing in the socket. This finding could be applicable for alveolar bone preservation after tooth extraction.

scholarly journals Replacement Process of Carbonate Apatite by Alveolar Bone in a Rat Extraction Socket

Materials ◽  
2021 ◽  
Vol 14 (16) ◽  
pp. 4457
Author(s):  
Xiaoxu Zhang ◽  
Ikiru Atsuta ◽  
Ikue Narimatsu ◽  
Nobuyuki Ueda ◽  
Ryosuke Takahashi ◽  
...  
Keyword(s):  
Bone Formation ◽  
Alveolar Bone ◽  
Autogenous Bone ◽  
Control Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Carbonate Apatite ◽  
Micro Computed Tomography ◽  
Extraction Socket ◽  
Bone Replacement ◽  
Significant Difference

The objective of this study was to investigate a bone graft substitute containing carbonate apatite (CO3Ap) to analyze bone replacement and the state of bone formation in vitro and in vivo compared with autogenous bone (AB) or control. An osteoclast precursor cell line was cultured with AB or CO3Ap, and morphological analysis using scanning electron microscopy and a tartrate-resistant acid phosphatase activity assay were performed. The right maxillary first and second molars of Wistar rats were extracted and compensated by AB or CO3Ap granules. Following implantation, the bone formation state was evaluated after 3, 5, 7, 14, and 28 days of surgery by micro-computed tomography and immunohistostaining. The osteoclast-like cell morphology was typical with many cell protrusions in the AB and CO3Ap groups. Additionally, the number of osteoclast-like cells formed in the culture increased in each group; however, there was no significant difference between the AB and CO3Ap groups. Five days after tooth extraction, osteoclasts were observed near CO3Ap. The bone thickness in the CO3Ap group was significantly increased than that in the control group and the bone formation in the CO3Ap group increased by the same level as that in the AB group. CO3Ap is gradually absorbed by osteoclasts in the extraction socket and is easily replaced by alveolar bone. The process of bone replacement by osteoclasts is similar to that of autologous bone. By observing the process of bone replacement in more detail, it may be possible to gain a better understanding of the bone formation and control the amount of bone after surgery.

scholarly journals Does Smoking Impair Bone Regeneration in the Dental Alveolar Socket?

2019 ◽  
Vol 105 (6) ◽  
pp. 619-629
Author(s):  
Furqan A. Shah ◽  
Shariel Sayardoust ◽  
Omar Omar ◽  
Peter Thomsen ◽  
Anders Palmquist
Keyword(s):  
Tooth Extraction ◽  
Alveolar Bone ◽  
Volume Ratio ◽  
Bone Microstructure ◽  
Matrix Composition ◽  
Micro Computed Tomography ◽  
Marginal Bone Loss ◽  
Mineral Density ◽  
Heavy Smoking ◽  
Bone Biopsies

Abstract Smoking is a major risk factor for dental implant failure. In addition to higher marginal bone loss around implants, the cellular and molecular responses to injury and implant physicochemical properties are also differentially affected in smokers. The purpose of this work is to determine if smoking impairs bone microstructure and extracellular matrix composition within the dental alveolar socket after tooth extraction. Alveolar bone biopsies obtained from Smokers (> 10 cigarettes per day for at least 10 years) and Ctrl (never-smokers), 7–146 months after tooth extraction, were investigated using X-ray micro-computed tomography, backscattered electron scanning electron microscopy, and Raman spectroscopy. Both Smokers and Ctrl exhibited high inter- and intra-individual heterogeneity in bone microstructure, which varied between dense cortical and porous trabecular architecture. Regions of disorganised/woven bone were more prevalent during early healing. Remodelled lamellar bone was predominant at longer healing periods. Bone mineral density, bone surface-to-volume ratio, mineral crystallinity, the carbonate-to-phosphate ratio, the mineral-to-matrix ratio, the collagen crosslink ratio, and the amounts of amino acids phenylalanine and proline/hydroxyproline were also comparable between Smokers and Ctrl. Bone microstructure and composition within the healing dental alveolar socket are not significantly affected by moderate-to-heavy smoking.

scholarly journals Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Structure ◽  
Precursor Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

scholarly journals Parathyroid hormone induces bone formation in phosphorylation-deficient PTHR1 knockin mice

2012 ◽  
Vol 302 (10) ◽  
pp. E1183-E1188 ◽  
Author(s):  
Nabanita S. Datta ◽  
Tareq A. Samra ◽  
Abdul B. Abou-Samra
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Physiological Role ◽  
Receptor Internalization ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Receptor Complexes ◽  
Diaphyseal Bone ◽  
Anabolic Action

Activation of G protein-coupled receptors by agonists leads to receptor phosphorylation, internalization of ligand receptor complexes, and desensitization of hormonal response. The role of parathyroid hormone (PTH) receptor 1, PTHR1, is well characterized and known to regulate cellular responsiveness in vitro. However, the role of PTHR1 phosphorylation in bone formation is yet to be investigated. We have previously demonstrated that impaired internalization and sustained cAMP stimulation of phosphorylation-deficient (PD) PTHR1 leads to exaggerated cAMP response to subcutaneous PTH infusion in a PD knockin mouse model. To understand the physiological role of receptor internalization on PTH bone anabolic action, we examined bone parameters of wild-type (WT) and PD knockin female and male mice following PTH treatment. We found a decrease in total and diaphyseal bone mineral density in female but not in male PD mice compared with WT controls at 3–6 mo of age. This effect was attenuated at older age groups. PTH administration displayed increased bone volume and trabecular thickness in the vertebrae and distal femora of both WT and PD animals. These results suggest that PTHR1 phosphorylation does not play a major role in the anabolic action of PTH.

Hyaluronic acid as an active agent to accelerate bone regeneration aftertooth extraction: a literature review

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Andyka Yasa I Putu Gede ◽  
I Made Jawi ◽  
I Made Muliarta
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
Bone Formation ◽  
Tooth Extraction ◽  
Alveolar Bone ◽  
Healing Process ◽  
Active Agent ◽  
Inflammatory Phase ◽  
Passive Mechanism ◽  
Active Mechanism

Tooth extraction is a dental treatment that is performed frequently in dentistry. This procedure will stimulate a sophisticated healing process involving a variety of biological factors although it takes a long time to complete. Three phases occur in this process i.e. the inflammatory phase, the proliferation phase, and the remodeling phase which aim to restore the tissue function. Several interventions can be used to accelerate bone formation after tooth extraction. Recently, hyaluronic acid (HA) has been commonly used in dentistry due to their essential physiological effects for the periodontal connective tissue, gingiva, and alveolar bone. Hyaluronic acidis a natural non-sulfate glycosaminoglycans compound that has high molecular weight consisting of D-glucuronic acid and N-acetylglucosamine. Hyaluronic acidis also a component of the extracellular matrix that plays an important role in morphogenesis and tissue healing. The mechanism of action of HA works in two ways, that is passive and active mechanism. The passive mechanism is depend on physical and chemical properties of HA that can change the molecular weight and concentration properties. The active mechanism of HA works by stimulating signal transduction pathway initiated by ligand binding with its receptors through autocrine or paracrine processes. The administration of HA can accelerate bone formation due to it can enhance bone morphogenetic protein (BMP) which belongs to the TGF- β superfamily that has high osteogenic capacity. The HA works through a passive mechanism that depends on its molecular weight and an active mechanism by increasing BMP activity.

The Effects of Signaling-Selective Parathyroid Hormone Analogs on Osteoporotic Osteocyte Apoptosis

2022 ◽  
Vol 12 (2) ◽  
pp. 316-322
Author(s):  
Meng-Sheng Song ◽  
Xiao Yu ◽  
Peng-Ze Rong ◽  
Qing-Jiang Pang
Keyword(s):  
Parathyroid Hormone ◽  
Immunohistochemical Staining ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Trabecular Thickness ◽  
Osteocyte Apoptosis ◽  
Trabecular Bone Microstructure ◽  
Hormone Analogs ◽  
Trabecular Number

Objectives: To compare the effects of signaling-selective parathyroid hormone analogs [G1, R19]hPTH(1–28) [GR(1–28)] and [G1, R19]hPTH(1–34) [GR(1–34)] on osteoporotic osteocyte apoptosis, and to explore the mechanism of the anti-osteoporotic difference. Methods: The osteoporosis model was established in eighty adult female C57BL/6 mice aged 12 weeks. The mice were subcutaneously administered with GR(1–28) and GR(1–34) 5 days per week for 8 weeks. Bilateral femur samples were collected at 4 and 8 weeks, and micro-computed tomography (CT), H&E staining and immunohistochemical staining analyses were performed. Results: From micro-CT analysis, GR(1–34) increased proximal femoral bone mineral density (BMD) and relative bone volume (BV/TV), which was higher than GR(1–28) did. In addition, more trabecular number (Tb.N), thinner trabecular thickness (Tb.Th) and wider trabecular separation (Tb.Sp) were measured at week 8 using GR(1–34). From H&E and immunohistochemical staining, a stronger apoptosis inhibition was induced by GR(1–34) with more Bcl-2 secretion but less Bax expression, as opposed to GR(1–28). Conclusions: GR(1–34) shows better anti-osteoporotic effects than GR(1–28), which appears to be attributed to the activation of the PLC-independent PKC signaling pathway triggered by the former, inhibiting osteocyte apoptosis through up-regulation of Bcl-2 and down-regulation of Bax to increase bone mass and improving trabecular bone microstructure to enhance bone quality by reducing trabecular number, increasing trabecular thickness and trabecular space.

scholarly journals Increased Marrow Adiposity in Premenopausal Women with Idiopathic Osteoporosis

2012 ◽  
Vol 97 (8) ◽  
pp. 2782-2791 ◽  
Author(s):  
Adi Cohen ◽  
David W. Dempster ◽  
Emily M. Stein ◽  
Thomas L. Nickolas ◽  
Hua Zhou ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Formation Rate ◽  
Premenopausal Women ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Marrow Fat ◽  
Bone Formation Rate ◽  
Idiopathic Osteoporosis ◽  
Marrow Adiposity

Abstract Context: We have previously reported that premenopausal women with idiopathic osteoporosis based on fractures (IOP) or idiopathic low bone mineral density (ILBMD) exhibit markedly reduced bone mass, profoundly abnormal trabecular microstructure, and significant deficits in trabecular bone stiffness. Bone remodeling was heterogeneous. Those with low bone turnover had evidence of osteoblast dysfunction and the most marked deficits in microstructure and stiffness. Objective: Because osteoblasts and marrow adipocytes derive from a common mesenchymal precursor and excess marrow fat has been implicated in the pathogenesis of bone fragility in anorexia nervosa, glucocorticoid excess, and thiazolidinedione exposure, we hypothesized that marrow adiposity would be higher in affected women and inversely related to bone mass, microarchitecture, bone formation rate, and osteoblast number. Design: We analyzed tetracycline-labeled transiliac biopsy specimens in 64 premenopausal women with IOP or ILBMD and 40 controls by three-dimensional micro-computed tomography and two-dimensional quantitative histomorphometry to assess marrow adipocyte number, perimeter, and area. Results: IOP and ILBMD subjects did not differ with regard to any adipocyte parameter, and thus results were combined. Subjects had substantially higher adipocyte number (by 22%), size (by 24%), and volume (by 26%) than controls (P &lt; 0.0001 for all). Results remained significant after adjusting for age, body mass index, and bone volume. Controls demonstrated expected direct associations between marrow adiposity and age and inverse relationships between marrow adiposity and bone formation, volume, and microstructure measures. No such relationships were observed in the subjects. Conclusions: Higher marrow adiposity and the absence of expected relationships between marrow adiposity and bone microstructure and remodeling in women with IOP or ILBMD suggest that the relationships between fat and bone are abnormal; excess marrow fat may not arise from a switch from the osteoblast to the adipocyte lineage in this disorder. Whether excess marrow fat contributes to the pathogenesis of this disorder remains unclear.

scholarly journals Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats

2018 ◽  
Vol 67 (3) ◽  
pp. 169-184 ◽  
Author(s):  
Tomoka Hasegawa ◽  
Tomomaya Yamamoto ◽  
Sadaoki Sakai ◽  
Yukina Miyamoto ◽  
Hiromi Hongo ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Biological Effects ◽  
Ovariectomized Rats ◽  
Sham Operation ◽  
Bone Surface ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Trabecular Thickness ◽  
Combined Administration

Summary Intermittent administration of human parathyroid hormone (1-34) (hPTH(1-34)) promotes anabolic action in bone by stimulating bone remodeling, while eldecalcitol, an analog of active vitamin D3, suppresses osteoclastic bone resorption, and forms new bone by minimodeling. We have examined the biological effects of combined administration of eldecalcitol and hPTH(1-34) on 9-week-old Wistar rats that underwent an ovariectomy (OVX) or Sham operation. They were divided into a Sham group, OVX with vehicle (OVX group), OVX with 10 µg/kg/day of hPTH(1-34) (PTH group), OVX with 20 ng/kg/day of eldecalcitol (eldecalcitol group) or OVX with 10 μg/kg/day of hPTH(1-34), and 20 ng/kg/day of eldecalcitol (combined group) for 4 or 8 weeks. As a consequence, the combined group showed a marked increase in bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) than OVX and had the highest bone mineral density (BMD) compared with other groups. OVX and PTH groups exhibited a high osteoblastic surface/bone surface (Ob.S/BS), mineral apposition rate (MAR), and bone formation rate/bone surface (BFR/BS) indices and many TRAP-reactive osteoclasts. Contrastingly, eldecalcitol and combined groups tended to attenuate the indices of osteoclastic surface/bone surface (Oc.S/BS) and Ob.S/BS than that the other groups. The combined group revealed histological profiles of minimodeling- and remodeling-based bone formation. Thus, the combined administration of eldecalcitol and hPTH(1-34) augments their anabolic effects by means of minimodeling and remodeling.

scholarly journals Low-dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent osteopenic mice

2014 ◽  
Vol 223 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Zuzana Saidak ◽  
Carole Le Henaff ◽  
Sofia Azzi ◽  
Caroline Marty ◽  
Pierre J Marie
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Low Dose ◽  
Standard Dose ◽  
Bone Microarchitecture ◽  
Bone Volume ◽  
Mineral Apposition Rate ◽  
Micro Computed Tomography ◽  
Trabecular Thickness ◽  
Osteoblast Activity

Intermittent administration of parathyroid hormone (PTH) 1–34 at a standard dose has been shown to induce anabolic effects in bone. However, whether low-dose PTH promotes bone formation during senescence is unknown. To address this issue, we determined the effects of low-dose PTH and analysed the underlying mechanisms in prematurely senescent mice that display osteopenia. Treatment of 9-week-old Samp6 mice for 6 weeks with PTH at a standard dose (100 μg/kg per day) increased vertebral and femoral bone mass and improved bone microarchitecture as a result of increased bone-forming surfaces and mineral apposition rate (MAR). At a tenfold lower dose (10 μg/kg per day), PTH increased axial bone volume and trabecular thickness, as detected by bone histomorphometry but not by micro-computed tomography analysis. This anabolic effect resulted from increased osteoblast activity, as reflected by increased serum N-terminal propeptide of type 1 procollagen (P1NP) levels and MAR, with unchanged bone-forming surface or osteoblast surface. Mechanistically, low-dose PTH increased the expression of osteoblast markers in bone marrow stromal cells and mature osteoblasts, which was associated with increased expression of the Wnt effector Wisp1. Moreover, low-dose PTH decreased the expression of the Mef2c transcription factor, resulting in decreased Sost expression in osteoblasts/osteocytes. These results indicate that PTH at a low dose is effective at promoting bone formation and increased bone volume in senescent osteopenic mice through increased osteoblast activity and modulation of specific Wnt effectors, which raises the potential therapeutic use of intermittent PTH at low dose to increase bone forming activity and bone mass in skeletal senescence.

Effects of Active Vitamin D or FGF23 Antibody on Hyp Mice Dentoalveolar Tissues

2021 ◽  
pp. 002203452110110
Author(s):  
E.J. Lira dos Santos ◽  
M.B. Chavez ◽  
M.H. Tan ◽  
F.F. Mohamed ◽  
T.N. Kolli ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Volume Fraction ◽  
Fibroblast Growth Factor 23 ◽  
Neutralizing Antibody ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Treatment Regimens ◽  
New Therapeutic Approaches ◽  
Phex Gene

Mutations in the PHEX gene lead to X-linked hypophosphatemia (XLH), a form of inherited rickets featuring elevated fibroblast growth factor 23 (FGF23), reduced 1,25-dihydroxyvitamin D (1,25D), and hypophosphatemia. Hyp mutant mice replicate the XLH phenotype, including dentin, alveolar bone, and cementum defects. We aimed to compare effects of 1,25D versus FGF23-neutralizing antibody (FGF23Ab) monotherapies on Hyp mouse dentoalveolar mineralization. Male Hyp mice, either injected subcutaneously with daily 1,25D or thrice weekly with FGF23 blocking antibody from 2 to 35 d postnatal, were compared to wild-type (WT) controls and untreated Hyp mice. Mandibles were analyzed by high-resolution micro–computed tomography (micro-CT), histology, and immunohistochemistry. Both interventions maintained normocalcemia, increased serum phosphate levels, and improved dentoalveolar mineralization in treated versus untreated Hyp mice. 1,25D increased crown dentin volume and thickness and root dentin/cementum volume, whereas FGF23Ab effects were limited to crown dentin volume. 1,25D increased bone volume fraction, bone mineral density, and tissue mineral density in Hyp mice, whereas FGF23Ab failed to significantly affect these alveolar bone parameters. Neither treatment fully attenuated dentin and bone defects to WT levels, and pulp volumes remained elevated regardless of treatment. Both treatments reduced predentin thickness and improved periodontal ligament organization, while 1,25D promoted a more profound improvement in acellular cementum thickness. Altered cell densities and lacunocanalicular properties of alveolar and mandibular bone osteocytes and cementocytes in Hyp mice were partially corrected by either treatment. Neither treatment normalized the altered distributions of bone sialoprotein and osteopontin in Hyp mouse alveolar bone. Moderate improvements from both 1,25D and FGF23Ab treatment regimens support further studies and collection of oral health data from subjects receiving a newly approved anti-FGF23 therapy. The inability of either treatment to fully correct Hyp mouse dentin and bone prompts further experiments into underlying pathological mechanisms to identify new therapeutic approaches.

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