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 Comparison of anterior and posterior trabecular bone microstructure of human mandible using cone-beam CT and micro CT

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Norliza Ibrahim ◽  
Azin Parsa ◽  
Bassam Hassan ◽  
Paul van der Stelt ◽  
Rabiah A. Rahmat ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Trabecular Bone ◽  
Structural Parameters ◽  
Cone Beam Ct ◽  
Imaging Systems ◽  
Cone Beam ◽  
Micro Computed Tomography ◽  
Trabecular Thickness ◽  
Trabecular Bone Microstructure ◽  
Trabecular Number

Abstract Background The aim of this study was to compare the trabecular bone microstructures of anterior and posterior edentulous regions of human mandible using cone-beam computed tomography (CBCT) and micro computed tomography (µCT). Methods Twenty volumes of interests consisting of six anterior and fourteen posterior edentulous regions were obtained from human mandibular cadavers. A CBCT system with a resolution of 80 µm (3D Accuitomo 170, J. Morita, Kyoto, Japan) and a µCT system with a resolution of 35 µm (SkyScan 1173, Kontich, Belgium) were used to scan the mandibles. Three structural parameters namely, trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were analysed using CTAn software (v 1.11, SkyScan, Kontich, Belgium). For each system, the measurements obtained from anterior and posterior regions were tested using independent sample t-test. Subsequently, all measurements between systems were tested using paired t-test. Results In CBCT, all parameters of the anterior and posterior mandible showed no significant differences (p > 0.05). However, µCT showed a significant different of Tb.Th (p = 0.023) between anterior and posterior region. Regardless of regions, the measurements obtained using both imaging systems were significantly different (p ≤ 0.021) for Tb.Th and Tb.N. Conclusions The current study demonstrated that only the variation of Tb.Th between anterior and posterior edentulous region of mandible can be detected using µCT. In addition, CBCT is less feasible than µCT in assessing trabecular bone microstructures at both regions.

scholarly journals Skeletal Effects of the Saturated 3-Thia Fatty Acid Tetradecylthioacetic Acid in Rats

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Astrid Kamilla Stunes ◽  
Irene Westbroek ◽  
Reidar Fossmark ◽  
Rolf Kristian Berge ◽  
Janne Elin Reseland ◽  
...  
Keyword(s):  
Whole Body ◽  
Sham Operation ◽  
Peroxisome Proliferator ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Peroxisome Proliferator Activated Receptor ◽  
Trabecular Thickness ◽  
Tetradecylthioacetic Acid ◽  
Femoral Metaphysis ◽  
Skeletal Effects

This study explores the skeletal effects of the peroxisome proliferator activated receptor (PPAR)pan agonist tetradecylthioacetic acid (TTA). Rats, without (Study I) and with ovariectomy (OVX) or sham operation (Study II), were given TTA or vehicle daily for 4 months. Bone markers in plasma, whole body and femoral bone mineral density and content (BMD and BMC), and body composition were examined. Histomorphometric and biomechanical analyses (Study I) and biomechanical and μCT analyses (Study II) of the femur were performed. Normal rats fed TTA had higher femoral BMD and increased total and cortical area in femur compared to controls. The ovariectomized groups had decreased BMD and impaired microarchitecture parameters compared to SHAM. However, the TTA OVX group maintained femoral BMC, trabecular thickness in the femoral head, and cortical volume in the femoral metaphysis as SHAM. TTA might increase BMD and exert a light preventive effect on estrogen-related bone loss in rats.

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.

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 RAGE supports parathyroid hormone-induced gains in femoral trabecular bone

2010 ◽  
Vol 298 (3) ◽  
pp. E714-E725 ◽  
Author(s):  
Binu K. Philip ◽  
Paul J. Childress ◽  
Alexander G. Robling ◽  
Aaron Heller ◽  
Peter P. Nawroth ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Mass ◽  
Bone Mineral ◽  
Cancellous Bone ◽  
Immunoglobulin Superfamily ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Bone Response ◽  
Accrual Rate ◽  
Underlying Mechanisms

Parathyroid hormone (PTH) restores bone mass to the osteopenic skeleton, but significant questions remain as to the underlying mechanisms. The receptor for advanced glycation end products (RAGE) is a multiligand receptor of the immunoglobulin superfamily; however, recent studies indicate a role in bone physiology. We investigated the significance of RAGE to hormone-induced increases in bone by treating 10-wk-old female Rage-knockout (KO) and wild-type (WT) mice with human PTH-(1–34) at 30 μg·kg−1·day−1 or vehicle control, 7 days/wk, for 7 wk. PTH produced equivalent relative gains in bone mineral density (BMD) and bone mineral content (BMC) throughout the skeleton in both genotypes. PTH-mediated relative increases in cortical area of the midshaft femur were not compromised in the null mice. However, the hormone-induced gain in femoral cancellous bone was significantly attenuated in Rage-KO mice. The loss of RAGE impaired PTH-mediated increases in femoral cancellous bone volume, connectivity density, and trabecular number but did not impact increases in trabecular thickness or decreases in trabecular spacing. Disabling RAGE reduced femoral expression of bone formation genes, but their relative PTH-responsiveness was not impaired. Neutralizing RAGE did not attenuate vertebral cancellous bone response to hormone. Rage-null mice exhibited an attenuated accrual rate of bone mass, with the exception of the spine, and an enhanced accrual rate of fat mass. We conclude that RAGE is necessary for key aspects of the skeleton's response to anabolic PTH. Specifically, RAGE is required for hormone-mediated improvement of femoral trabecular architecture but not intrinsically necessary for increasing cortical thickness.

scholarly journals ­­­­­Comparison of Anterior and Posterior Trabecular Bone Microstructure of Human Mandible Using Cone-Beam CT and Micro CT

2020 ◽  
Author(s):  
Norliza Ibrahim ◽  
Azin Parsa ◽  
Bassam Hassan ◽  
Paul der Stelt ◽  
Siti Mazlipah Ismail ◽  
...  
Keyword(s):  
Trabecular Bone ◽  
Structural Parameters ◽  
Cone Beam Ct ◽  
Bone Microstructure ◽  
Imaging Systems ◽  
Cone Beam ◽  
Micro Ct ◽  
Trabecular Thickness ◽  
Trabecular Bone Microstructure ◽  
Trabecular Number

Abstract Objective The aim of this study was to compare the trabecular bone microstructures of anterior and posterior edentulous regions of human mandible using cone-beam CT (CBCT) and micro CT (µCT).Materials and methods Twenty volumes of interests consisting of six anterior and fourteen posterior edentulous regions were obtained from human mandibular cadavers. A CBCT system with a resolution of 80 µm (3D Accuitomo 170, J. Morita, Kyoto, Japan) and a µCT system with a resolution of 35 µm (SkyScan 1173, Kontich, Belgium) were used to scan the mandibles. Three structural parameters namely, trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were analysed using CTAn software (v 1.11, SkyScan, Kontich, Belgium). For each system, the measurements obtained from anterior and posterior regions were tested using independent sample t-test. Subsequently, all measurements between systems were tested using paired t-test.Results In CBCT, all parameters of the anterior and posterior mandible showed no significant differences (p > 0.05). However, µCT showed a significant different of Tb.Th (p = 0.023) between anterior and posterior region. Regardless of regions, the measurements obtained using both imaging systems were significantly different (p ≤ 0.021) for Tb.Th and Tb.N.Conclusions The current study demonstrated that only the variation of Tb.Th between anterior and posterior edentulous region of mandible can be detected using micro CT. In addition, CBCT is less feasible than micro CT in assessing trabecular bone microstructures at both regions.

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.

Regionally specific compensation for bone loss in the tibial trabeculae of estrogen-deficient rats

2007 ◽  
Vol 48 (5) ◽  
pp. 531-539 ◽  
Author(s):  
Z. F. Sheng ◽  
R. C. Dai ◽  
X. P. Wu ◽  
L. N. Fang ◽  
H. J. Fan ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Mineral ◽  
Estrogen Deficiency ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Sprague Dawley Rats ◽  
Rat Tibia

Background: Bone mineral density (BMD) and microstructural variations have been extensively investigated in recent years; however, the compensation for bone loss between different regions is still unclear. Purpose: To fully characterize regional variations in bone mineral density (BMD) as well as the microstructure and dynamic changes of rat tibial trabeculae that occur with bone loss associated with estrogen deficiency. Material and Methods: Female Sprague-Dawley rats were ovariectomized (OVX), sham-operated (sham), or left unoperated (baseline control). The left tibiae were harvested at baseline, and at postoperative weeks 3 and 15. High-resolution micro-computed tomography (µCT) was used to identify the densitometric and microstructural properties of trabeculae in the proximal ends of the rat tibia, specifically the epiphysis and metaphysis. Results: Volumetric BMDs at the organ (organ BMD) and tissue (tissue BMD) levels were significantly higher for trabeculae at the epiphysis than metaphysis. Moreover, trabeculae at the epiphysis were thicker, and fewer in number and connectivity than those at the metaphysis, which were more rod like. Trabeculae at the metaphysis were more susceptible to bone loss induced by estrogen deprivation than at the epiphysis, and the regions varied greatly in their adaptation to this loss. At the metaphysis, trabecular tissue BMD and thickness were unexpectedly higher at postoperative week 15 than week 3 or baseline. In contrast, at the epiphysis, tissue BMD did not change with time, but trabecular thickness significantly increased at week 15 compared to baseline and was also greater in OVX compared to sham rats. Conclusion: Metaphyseal and epiphyseal trabeculae show regionally specific variations in BMD and microstructure. The former are more susceptible to bone loss induced by estrogen deficiency and would be strengthened by either hypertrophy or hypermineralization, while epiphyseal trabeculae are mainly strengthened by thickening.

Assessment of Bone Regeneration Using Tooth Ash and Injectable Platelet Rich Fibrin: A Microcomputed Tomographic (CT) Analysis

2021 ◽  
Vol 11 (5) ◽  
pp. 793-804
Author(s):  
Saleh Alshihri ◽  
Mohammed Kindi ◽  
Randa Alfotawi ◽  
Marium Al Hindi ◽  
Osama Alghamdi ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Micro Ct ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Socket Preservation ◽  
Platelet Rich Fibrin ◽  
The Mean ◽  
Trabecular Separation ◽  
Trabecular Number

Introduction: One of the main challenge of bone graft or socket preservation in particular is to get good quality and quantity of bone in short time prior to implant bed preparation. The buccal bone at the crest of the ridge is a very thin bone and usually resorb faster than the rest of alveolar bone which may hinder an optimum dento-osseous implant insertion. The purpose of this study will be to assess the bone regeneration capabilities of Tooth Ash Particles (TAP) with injectable Plasma Rich Fibrin (i-PRF) and Tooth Ash Particles (TAP) alone at defects created in the goat mandible bone using micro-computed tomographic (micro-CT). Materials and Methods: A total, 54 bone defect (5 mm × 8 mm) were performed in the 18 goats. The created defect received different treatment (Tx): Tx.A: Unfilled defect (allow natural bone regeneration; Tx.B: Tooth Ash particle (TAP) alone; Tx.C: Tooth Ash + injectable PRF (TAP/i-PRF). Six goats, were sacrificed at different time points:Group 1: at 2nd week, Group2: at 5th week and Group3 at 8th week. The newly formed bone (NFB) was analyzed using micro-CT at different time points. Quantitative and qualitative assessment were carried out namely; the volume of new bone formation (NF-BV) within the defect and its mineral density (NF-BMD), Trabecular Thickness (Tb Th), Trabecular Number (Tb N) and Trabecular Separation (Tb Sp). Result: By 8th week, the mean NF-BV was 69.482 ± 6.554 mm3 (cubic millimeter), 65.872±6.804 mm3, 26.820±14.643 mm3, while the mean NF-BMD was 0.417±0.119g/mm3, 0.786±0.036 g/mm3, 0.805±0.033 g/mm3 for the defects which received Tx.C, Tx.B and Tx.A respectively. At 8th weekTb Th of NFB was 0.612±0.168, 0.913±0.112, and 0.701 ±0.126, Trabecular Number of NFB was 2.062±0.946, 1.002±0.155, and 1.816±2.042 and, Trabecular Separation of NFB was 0.330 ±0.131, 0.559 ±0.110, and 0.495 ±0.258 for the defects which received Tx.A, Tx.B and Tx.C respectively. Conclusion: Micro-CT study demonstrated that tooth ash particles mixed with injectable Platelet Rich Fibrin (i-PRF) on mandibular bone defect in goat’s model, resulting in new bone with significantly higher volume, mineral density and less remodeling rate when compared with normal bone regeneration of unfilled defects.

scholarly journals Prolonged low-dose infusion of human parathyroid hormone does not increase femoral cancellous bone volume in ovariectomized rats

1999 ◽  
pp. 70-74 ◽  
Author(s):  
P Morley ◽  
JF Whitfield ◽  
GE Willick ◽  
V Ross ◽  
S MacLean ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cancellous Bone ◽  
Oral Delivery ◽  
Bone Growth ◽  
Bone Volume ◽  
Ovariectomized Rats ◽  
Low Doses ◽  
Human Parathyroid Hormone ◽  
Trabecular Thickness ◽  
Trabecular Number

OBJECTIVE: Daily injections of human parathyroid hormone (hPTH) increase bone volume in various animal species and in osteoporotic women. For hPTH to be widely accepted as an anabolic therapy for treating postmenopausal osteoporosis alternative delivery options need to be explored to replace the need for daily patient subcutaneous self-injection. Among these are inhalation, oral delivery and the use of programmable implanted minipumps to deliver the peptide. While infusion of high doses of PTH causes bone loss and hypercalcemia, no studies have assessed the effects of prolonged infusion of low doses of PTH on bone growth. DESIGN AND METHODS: [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2) was delivered by Alzet minipumps to ovariectomized rats for 6 weeks after which histomorphometric indices (cancellous bone volume, trabecular thickness, mean trabecular number) of bone formation were measured in distal femurs. RESULTS: Infusing low doses (0.05 and 0.1 nmole/100g body weight/day) of the hPTH analog, [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2), for 6 weeks does not prevent the ovariectomy-induced loss of rat femoral cancellous bone volume, trabecular thickness or trabecular number. CONCLUSION: These results support the absolute requirement of daily injections for the osteogenic action of hPTH on bone.

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