scholarly journals Parathyroid hormone (1-34) ameliorates cartilage degeneration and subchondral bone deterioration in collagenase-induced osteoarthritis model in mice

2020 ◽  
Vol 9 (10) ◽  
pp. 675-688
Author(s):  
Li-tao Shao ◽  
Yu Gou ◽  
Jia-kang Fang ◽  
Yun-peng Hu ◽  
Qiang-qiang Lian ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Mouse Model ◽  
Subchondral Bone ◽  
Signalling Pathway ◽  
Dependent Manner ◽  
Micro Ct ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Significant Difference ◽  
Stat3 Signalling

Aims Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Methods Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Results Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Conclusion Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688.

scholarly journals Evaluation of the effect of vitamin D3 on mandibular condyles in an ovariectomized mouse model: a micro-CT study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Szandra Körmendi ◽  
Bálint Vecsei ◽  
Szilvia Ambrus ◽  
Kaan Orhan ◽  
Csaba Dobó-Nagy
Keyword(s):  
Mouse Model ◽  
Trabecular Bone ◽  
Vitamin D3 ◽  
Sham Group ◽  
Mandibular Condyle ◽  
Bone Microstructure ◽  
Micro Ct ◽  
Trabecular Thickness ◽  
Ovariectomized Mouse ◽  
Significant Difference

Abstract Background This study aimed to investigate the effect of ovariectomy and vitamin D3 on bone microstructure; this effect was examined in three regions of interest at one femoral and two mandibular sampling sites bone in an ovariectomized mouse model. Methods Thirty-six week-old female mice were randomly divided into three groups: 10 subjects were given oral cholecalciferol (vitamin D3) daily for 6 weeks after undergoing bilateral ovariectomy (D3 group), while 10 ovariectomized subjects (OVX) and 10 subjects who underwent a sham operation (SHAM) received peanut oil daily during the investigation. After extermination, the left hemimandible and femur were removed and scanned by micro-CT. The bone micromorphology parameters were analyzed and the BMD was calculated. Results The bone volume fraction (BV/TV) was significantly lower in the trabecular bone of the mandibular condyle in the OVX group than in the SHAM and D3 groups. Also there was a significant difference between the SHAM and D3 groups. The specific bone surface (BS/BV) was significantly higher in the OVX and D3 groups than in the SHAM group. Trabecular thickness (Tb.Th) was significantly higher in the SHAM group, and the trabecular bone pattern factor (Tb.Pf) was significantly higher in the OVX group than in the other two groups. Bone mineral density (BMD) of the femur and the mandible was significantly lower in the OVX group than in the SHAM and D3 groups. Conclusions Our results show that ovariectomy causes a significantly weaker bone microstructure in the mandibular condyle, where the protective effect of vitamin D3 resulted in a partial resorption.

scholarly journals Using Transgenic Mice to Explore the Effect of il-17rc Gene Knockout on Bone Metabolism

2021 ◽  
Author(s):  
Fan Yu ◽  
Bo Li ◽  
Guoliang Zhang ◽  
Song Zhou
Keyword(s):  
Transgenic Mice ◽  
Bone Metabolism ◽  
Gene Knockout ◽  
Control Group ◽  
Signal Pathways ◽  
Interleukin 17 ◽  
Micro Ct ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Significant Difference

Abstract ObjectiveTo investigate whether interleukin-17 receptor C (il-17rc) gene knockout leads to systemic osteoporosis in transgenic mice. MethodsThe immunohistochemistry and micro computed tomography (micro-CT) were used to analyze the condition of vertebral cancellous bone in 3-month healthy female wild-type C57BL/6 mice (control group) and il-17rc gene knockout C57BL/6 mice (experimental group). ResultsWild type C57BL/6 mice had higher bone density per unit volume (0.52 ± 0.12 vs. 0.47 ± 0.05, P = 0.028) (g/cm3), more trabecular connections (8.97 ± 1.46 vs. 5.59 ± 3.15, P = 0.017) (1/mm), thicker trabecular thickness (0.16 ± 0.08 vs. 0.10 ± 0.04, P = 0.029) (1/mm) and the number of trabeculae was more (5.01 ± 0.33 vs. 3.16 ± 0.37, P = 0.038) (1/mm) than mut-il-17rc mice. In addition, the results of micro-CT also showed that the osteoporosis of il-17rc gene knockout C57BL/6 mice was mainly manifested in T13 (P = 0.039), L1 (P = 0.035), L3 (P = 0.018), L5 (P = 0.021) and L6 (P = 0.036), but the mean bone mineral density between L2 (P = 0.317) and L4 (P = 0.242) was no significant difference between the two groups. ConclusionIL-17/il-17rs signal axis is widely distributed in the animal skeletal system and is one of the important signal pathways regulating bone metabolism. Knockout of il-17rc gene can lead to the occurrence of osteoporosis in model animals.

scholarly journals Does Bisphosphonate Increase the Sclerosis of Tibial Subchondral Bone in the Progression of Knee Osteoarthritis—A Propensity Score Matching Cohort Study Based on Osteoarthritis Initiative

2021 ◽  
Vol 8 ◽  
Author(s):  
Mingyang Li ◽  
Yong Nie ◽  
Yi Zeng ◽  
Yuangang Wu ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Physical Activity ◽  
Knee Osteoarthritis ◽  
Subchondral Bone ◽  
Volume Fraction ◽  
Short Form ◽  
Activity Level ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Significant Difference ◽  
Osteoarthritis Initiative

Bisphosphonate has great potential in KOA therapy, but whether the anti-resorption mechanism of bisphosphonate aggravates sclerosis of subchondral bone remains unclear. We found that bisphosphonate use did not increase sclerosis of subchondral bone in established KOA, perhaps resolving some concerns about bisphosphonate in patients with KOA.Introduction: Most studies have focused on the protective effect of bisphosphonate on early knee osteoarthritis (KOA) through its anti-resorption mechanism in osteoclasts. However, late KOA has a decreased rate of resorption, which is the opposite of early KOA. The risk of subchondral bone sclerosis in late KOA after using bisphosphonate has not been investigated using morphometry.Methods: Forty-five patients who had ever used bisphosphonate (or 33 patients with current use) were matched with controls through propensity matching methods, including age, body mass index (BMI), sex, health status (12-Item Short Form Survey physical health score), physical activity level (Physical Activity Scale for the Elderly score), vitamin D use, and calcium use. At the baseline and 12-month (or 18-month) follow-up, bone mineral density (BMD) of the tibia and hip was measured by dual-energy X-ray absorptiometry (DXA), and medial tibial subchondral bone morphometry: bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated based on 3-T trabecular MRI. Data were obtained from the Bone Ancillary Study in the Osteoarthritis Initiative (OAI) project.Results: The yearly percentage change in hip BMD of the current bisphosphonate-use group was significantly greater than that of the non-bisphosphonate-use group (0.7% vs. −1%, P = 0.02). The other outcomes (BV/TV, Tb.N, Tb.Sp, Tb.Th, tibia medial BMD, and tibia lateral BMD) between the two groups presented no significant difference. The non-bisphosphonate-use group experienced a significant increase in Tb.Th [2%, 95% CI = (1%, 4%), P = 0.01], while the bisphosphonate-use group presented no significant change [1%, 95% CI = (−2%, 4%), P = 0.54].Conclusions: Bisphosphonate use did not increase sclerosis of subchondral bone in established KOA. Bisphosphonate might have a stage-dependent effect on subchondral bone in KOA initiation and progression.

scholarly journals Micro-Computed Tomography Analysis of Subchondral Bone Regeneration Using Osteochondral Scaffolds in an Ovine Condyle Model

2021 ◽  
Vol 11 (3) ◽  
pp. 891
Author(s):  
Taylor Flaherty ◽  
Maryam Tamaddon ◽  
Chaozong Liu
Keyword(s):  
Computed Tomography ◽  
Bone Regeneration ◽  
Subchondral Bone ◽  
Volume Ratio ◽  
Bone Volume ◽  
Osteochondral Defects ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Trabecular Thickness ◽  
Osteochondral Scaffold

Osteochondral scaffold technology has emerged as a promising therapy for repairing osteochondral defects. Recent research suggests that seeding osteochondral scaffolds with bone marrow concentrate (BMC) may enhance tissue regeneration. To examine this hypothesis, this study examined subchondral bone regeneration in scaffolds with and without BMC. Ovine stifle condyle models were used for the in vivo study. Two scaffold systems (8 mm diameter and 10 mm thick) with and without BMC were implanted into the femoral condyle, and the tissues were retrieved after six months. The retrieved femoral condyles (with scaffold in) were examined using micro-computed tomography scans (micro-CT), and the micro-CT data were further analysed by ImageJ with respect to trabecular thickness, bone volume to total volume ratio (BV/TV) ratio, and degree of anisotropy of bone. Statistical analysis compared bone regeneration between scaffold groups and sub-set regions. These results were mostly insignificant (p < 0.05), with the exception of bone volume to total volume ratio when comparing scaffold composition and sub-set region. Additional trends in the data were observed. These results suggest that the scaffold composition and addition of BMC did not significantly affect bone regeneration in osteochondral defects after six months. However, this research provides data which may guide the development of future treatments.

scholarly journals P114 Effect of vitamin D on parathyroid hormone, serum calcium and bone mineral density in patients with primary hyperparathyroidism being managed conservatively

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Mahrukh Khalid ◽  
Vismay Deshani ◽  
Khalid Jadoon
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Primary Hyperparathyroidism ◽  
Bone Mineral ◽  
Serum Calcium ◽  
Mineral Density ◽  
Neck Of Femur ◽  
Vitamin D Levels ◽  
Significant Difference

Abstract Background/Aims  Vitamin D deficiency is associated with more severe presentation of primary hyperparathyroidism (PTHP) with high parathyroid hormone (PTH) levels and reduced bone mineral density (BMD). We analyzed data to determine if vitamin D levels had any impact on PTH, serum calcium and BMD at diagnosis and 3 years, in patients being managed conservatively. Methods  Retrospective analysis of patients presenting with PHPT. Based on vitamin D level at diagnosis, patients were divided into two groups; vitamin D sufficient (≥ 50 nmol/L) and vitamin D insufficient (≤ 50 nmol/L). The two groups were compared for age, serum calcium and PTH levels at diagnosis and after mean follow up of 3 years. BMD at forearm and neck of femur (NOF) was only analyzed in the two groups at diagnosis, due to lack of 3 year’s data. Results  There were a total of 93 patients, 17 males, mean age 70; range 38-90. Mean vitamin D level was 73.39 nmol/L in sufficient group (n = 42) and 34.48 nmol/L in insufficient group (n = 40), (difference between means -38.91, 95% confidence interval -45.49 to -32.33, p &lt; 0.0001). There was no significant difference in age, serum calcium and PTH at the time of diagnosis. After three years, there was no significant difference in vitamin D levels between the two groups (mean vitamin D 72.17 nmol/L in sufficient group and 61.48 nmol/L in insufficient group). Despite rise in vitamin D level in insufficient group, no significant change was observed in this group in PTH and serum calcium levels. BMD was lower at both sites in vitamin D sufficient group and difference was statistically significant at NOF. Data were analyzed using unpaired t test and presented as mean ± SEM. Conclusion  50% of patients presenting with PHPT were vitamin D insufficient at diagnosis. Vitamin D was adequately replaced so that at 3 years there was no significant difference in vitamin D status in the two groups. Serum calcium and PTH were no different in the two groups at diagnosis and at three years, despite rise in vitamin D levels in the insufficient group. Interestingly, BMD was lower at forearm and neck of femur in those with sufficient vitamin D levels and the difference was statistically significant at neck of femur. Our data show that vitamin D insufficiency does not have any significant impact on PTH and calcium levels and that vitamin D replacement is safe in PHPT and does not impact serum calcium and PTH levels in the short term. Lower BMD in those with adequate vitamin D levels is difficult to explain and needs further research. Disclosure  M. Khalid: None. V. Deshani: None. K. Jadoon: None.

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.

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 P0869EXOGENOUS OSTEOGENIC FACTOR 1 ADMINISTRATION ATTENUATED VASCULAR CALCIFICATION AND IMPROVED BONE DISORDERS IN CHRONIC UREMIC RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chien-Te Lee ◽  
Hwee-Yeong Ng ◽  
Wen-Lin Chen ◽  
Yuai-Ting Lee
Keyword(s):  
Renal Failure ◽  
Vascular Calcification ◽  
Fibroblast Growth Factor 23 ◽  
Mineral Density ◽  
Bone Disorders ◽  
Trabecular Thickness ◽  
Bony Structure ◽  
Significant Difference ◽  
Fgf 23 ◽  
Osteogenic Factor

Abstract Background and Aims Hyperphosphatemia and secondary hyperparathyroidism are frequent complications in chronic kidney disease (CKD) which both contribute to increased morbidity and mortality in CKD. Osteogenic factor-1 (OP-1) is an important member of BMPs subfamily and its effects on CKD-associated mineral and bone disorders (MBD) is controversial. The study examined whether exogenous OP-1 administration can modulate disturbed CKD-MBD in adenine-induced chronic uremic rats Method Chronic renal failure was induced in adult male SD rats by feeding adenine-containing diet. After adenine diet feeding 3 weeks, animals were injected with OP-1 (5μg/kg/day) intraperitoneally for 2 weeks. The serum and urine phosphorus levels and associated mineral parameters, including fibroblast growth factor 23(FGF-23), DKK-1 and sclerostin were measured. Vascular calcification was assessed by immunohistochemistry staining on aortic tissue. Bony structure was evaluated by microCT (Bruker-microCT, Kontich, Belgium). Results A significant decrease of body weight and deteriorated renal function was observed in adenine and OP-1 treatment groups during study period and serum creatinine levels were similar (5.23 ±1.1 mg/dL vs. 5.4 ±1.2 mg/dL, p&gt;0.05). Animals in OP-1 group had lower serum phosphorous (18.7±5.1 vs. 29.0±9.6 mg/dL, p&lt;0.05) and intact parathyroid hormone levels (2906.1±1206.9 vs. 4669.7±2505.9 pg/dL, p&lt;0.05) compared to adenine group. Decreased urine phosphorous excretion was noted in both groups without significant difference. Levels of serum FGF-23, sclerostin and DKK-1 were significantly lower in OP-1 treatment group (all p&lt; 0.05). OP-1 administration diminished the staining of RUNX2 (59.1±3% of adenine-treated group), alkaline-phosphatase (49.4±5.7%), β-caterin (39.3±1.8%), BMP2 (43.2%±6.7%), and BMP7 (51.9±10%, all p &lt;0.05). MicroCT revealed that bone mineral density was increased by OP-1 treatment (0.46±0.1 vs.0.39±0.06 g/cm3). Total volume was increased but bone volume was not changed. OP-1 administration did not affect trabecular thickness and trabecular number. Conclusion Our data indicated administration of exogenous OP-1 improved hyperparathyroidism and attenuated vascular calcification. OP-1 treatment was also associated with beneficial effects on bony structure in animals with renal failure.

scholarly journals The Potential Role of Wedololactone in Treating Particle-induced Osteolysis _A Mouse Calvarial Model

2021 ◽  
Author(s):  
Yung-Chang Lu ◽  
Ting-Kuo Chang ◽  
Tzu-Chiao Lin ◽  
Shu-Ting Yeh ◽  
Hsu-Wei Fang ◽  
...  
Keyword(s):  
Potential Role ◽  
Histological Analysis ◽  
Total Joint Replacement ◽  
Disease Model ◽  
Potential Treatment ◽  
Micro Ct ◽  
Mineral Density ◽  
Clinical Complications ◽  
Significant Difference

Abstract Background: Osteolysis is one of the most prevalent clinical complications of total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the use of WDL as a potential treatment for reducing the risk of particle-induced osteolysis using a well-established particle-induced mice calvarial disease model. Methods: Thirty-two C57BL/6J mice were randomized into four groups: sham, polystyrene particles (PS), PS particles with WDL treatment for 4 weeks (WDL 4w) and PS particles with WDL treatment for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mass. Osteoclast numbers were also measured from histological analysis. Results: The results showed that bone mineral density was significantly higher in the WDL 8w group than in the PS group (p < 0.05), and both the WDL 4 and WDL 8w groups had lower osteoclast numbers (p < 0.05). No significant difference in osteoclast number was found between the WDL 4w and WDL 8w groups. Conclusions: These results support the use of WDL as a herbal medicine for reducing the severity of particle-induced osteolysis after TJR.

scholarly journals Lansoprazole-Induced Osteoporosis via IP3R and SOCE Mediated Calcium Signaling Pathway

2021 ◽  
Author(s):  
Zi-Ping Cheng ◽  
Jie-Yang Liu ◽  
Meng-Yuan Ma ◽  
Shi-Yu Sun ◽  
Zeng-qing Ma ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Vehicle Group ◽  
Dependent Manner ◽  
Micro Ct ◽  
Mineral Density ◽  
Calcium Release Channel ◽  
Blood Calcium ◽  
Term Administration

Abstract Background: Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purposes of this study were to establish a murine model of chronic oral administration of PPIs to verify whether PPIs caused bone metabolic impairment, and to investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 mouse osteoblasts.Methods: Lansoprazole-induced bone loss model was employed to investigate the damage effects of PPIs. In vivo, immunohistochemistry and HE staining, micro-CT analysis, blood biochemical tests were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects and related signaling pathway of lansoprazole on MC3T3-E1 cells were investigated by CCK8, EDU kit, flow cytometry, laser confocal, patch clamp, PCR and Western blotting, etc.Results: After 6 months of lansoprazole gavage in ICR mice, micro-CT results showed that compared with the vehicle group, the bone mineral density (BMD) of high-dose group was significantly decreased (P<0.05), and the bone microarchitecture gradually degraded. Biochemical assay of bone serum found that blood calcium and phosphorus were both decreased (P<0.01). We found that long-term administration of lansoprazole impairs skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOC pathway, efctively blocked calcium increase caused by LPZ, thus protecting cell viability.Conclusion: Long-term administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium elevation in osteoblasts in a concentration dependent manner, intracellular calcium ([Ca2+] persisted at a high concentration thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblasts apoptosis.

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