BACKGROUNDTitanium nanoparticle (TP) migration into peri-implant bone may influence osseointegration. It remains unclear how loading protocols may affect TP distribution. This study aimed to detect TP in the bone around implants undergoing different loading protocols in Macaca fascicularis.METHODSNine histological samples containing 21 implants with two loading groups were analyzed. In the delayed-loaded (DL) group (n = 16), the implants were loaded after 3 months and retrieved after 3 months, and in the immediately loaded (IL) group (n = 5), they were loaded on the day of surgery and retrieved after 3 months. Environmental scanning electron microscopy (ESEM) grayscale-level detection and energy-dispersive X-ray spectroscopy (EDX) microchemical analysis were used to assess TP and bone mineralization. Regions of interest (ROI) located at the implant coronal/apical portion (100×) and at the bone-implant interface (1000×) were selected. Bone area distribution (mean% ± SD%) and titanium content were analyzed using two-way analysis of variance (ANOVA) (p < 0.05).RESULTSTitanium granules (2-10 µm) were detected in all regions, with a higher prevalence in the coronal portions of DL implants. In IL implant sections, bone closer to the implants showed a lower prevalence of titanium (p < 0.05). EDX analysis demonstrated a decreasing trend in titanium from the nearest areas to those more distant (up to 2.0 mm). DL implants exhibited lower percentages of mineralized bone compared to IL implants in the coronal portion (mean values 31.0 ± 13.7 and 11.6 ± 2.8) (p < 0.05). IL implants showed a higher percentage of mineralized bone (p < 0.05) in the apical region (mean values 51.8 ± 15.5 and 32.2 ± 15.6).CONCLUSIONTP were widely present in bone tissues adjacent to the implant surface, particularly at the coronal bone. In the coronal portion of the DL group, a less mineralized bone area was observed compared to the IL group, suggesting higher bone remodeling activities.PLAIN LANGUAGE SUMMARYTitanium particles were widely present in bone tissues adjacent to the implant areas, with greater distribution observed in regions experiencing significant wear (i.e., the coronal portion of the cortical bone), likely due to surgical insertion and related procedures.
{"title":"Titanium migration and bone response in loaded osseointegrated implants: ESEM-EDX analysis in Macaca fascicularis.","authors":"Fausto Zamparini,Andrea Spinelli,Maria Giovanna Gandolfi,Stefano Chersoni,Achille Tarsitano,Giovanni Badiali,Chooi Gait Toh,Carlo Prati,Georgios Romanos","doi":"10.1002/jper.70003","DOIUrl":"https://doi.org/10.1002/jper.70003","url":null,"abstract":"BACKGROUNDTitanium nanoparticle (TP) migration into peri-implant bone may influence osseointegration. It remains unclear how loading protocols may affect TP distribution. This study aimed to detect TP in the bone around implants undergoing different loading protocols in Macaca fascicularis.METHODSNine histological samples containing 21 implants with two loading groups were analyzed. In the delayed-loaded (DL) group (n = 16), the implants were loaded after 3 months and retrieved after 3 months, and in the immediately loaded (IL) group (n = 5), they were loaded on the day of surgery and retrieved after 3 months. Environmental scanning electron microscopy (ESEM) grayscale-level detection and energy-dispersive X-ray spectroscopy (EDX) microchemical analysis were used to assess TP and bone mineralization. Regions of interest (ROI) located at the implant coronal/apical portion (100×) and at the bone-implant interface (1000×) were selected. Bone area distribution (mean% ± SD%) and titanium content were analyzed using two-way analysis of variance (ANOVA) (p < 0.05).RESULTSTitanium granules (2-10 µm) were detected in all regions, with a higher prevalence in the coronal portions of DL implants. In IL implant sections, bone closer to the implants showed a lower prevalence of titanium (p < 0.05). EDX analysis demonstrated a decreasing trend in titanium from the nearest areas to those more distant (up to 2.0 mm). DL implants exhibited lower percentages of mineralized bone compared to IL implants in the coronal portion (mean values 31.0 ± 13.7 and 11.6 ± 2.8) (p < 0.05). IL implants showed a higher percentage of mineralized bone (p < 0.05) in the apical region (mean values 51.8 ± 15.5 and 32.2 ± 15.6).CONCLUSIONTP were widely present in bone tissues adjacent to the implant surface, particularly at the coronal bone. In the coronal portion of the DL group, a less mineralized bone area was observed compared to the IL group, suggesting higher bone remodeling activities.PLAIN LANGUAGE SUMMARYTitanium particles were widely present in bone tissues adjacent to the implant areas, with greater distribution observed in regions experiencing significant wear (i.e., the coronal portion of the cortical bone), likely due to surgical insertion and related procedures.","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":"14 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaolin Li, Yujun Jiang, Minglei Zhang, Hongrui Liu, Minqi Li
<p><strong>Background: </strong>CD4<sup>+</sup> T lymphocytes play a central role in the pathogenesis of periodontitis, with the Treg/Th17 (regulatory T cell/T helper 17 cell) imbalance closely linked to diabetes-associated periodontitis (DPD). Maxacalcitol (OCT), an analog of active vitamin D, has therapeutic effects on diseases involving Treg/Th17 imbalance. This study aimed to determine whether OCT improved DPD by restoring the Treg/Th17 imbalance via store-operated Ca<sup>2+</sup> entry (SOCE)-mediated mitochondrial dysfunction.</p><p><strong>Methods: </strong>The DPD model was established in male C57BL/6 mice and treated with local injections or oral administration of OCT. Microcomputed tomography and flow cytometry were used to assess the alveolar bone, Treg/Th17 balance, and SOCE. Flow cytometry and transmission electron microscopy were applied to detect Treg/Th17 balance and mitochondrial function.</p><p><strong>Results: </strong>OCT attenuated alveolar bone loss and Treg/Th17 imbalance and enhanced the expressions of SOCE components in mice with DPD, with local injections showing more pronounced effects than oral administration. Furthermore, OCT restored the Treg/Th17 balance and improved mitochondrial dysfunction and overactivation of SOCE caused by lipopolysaccharides and high glucose. Additionally, SOCE inhibitors ameliorated mitochondrial abnormalities and Treg/Th17 imbalance under DPD conditions, whereas mitochondrial toxin and SOCE activators abolished the beneficial effects of OCT.</p><p><strong>Conclusions: </strong>OCT ameliorates Treg/Th17 imbalance via SOCE-mediated mitochondrial function, thereby effectively improving DPD.</p><p><strong>Plain language summary: </strong>Periodontitis, an inflammatory condition causing bone loss around teeth, is often more severe in individuals with diabetes due to immune system dysfunction. Specifically, diabetes-associated periodontitis (DPD) involves an imbalance between two types of immune cells: regulatory T cells (Treg), which control inflammation, and T helper 17 cells (Th17), which promote inflammation. This study explored how maxacalcitol (1α,25-dihydroxy-22-oxacalcitriol, OCT), a synthetic analog of active vitamin D3, treats DPD by correcting this immune cell imbalance. Using mouse models of DPD, we found that OCT significantly reduced bone loss and restored the balance between Treg and Th17 cells. Further investigation demonstrated that OCT functions by controlling calcium (Ca<sup>2</sup>⁺) entry into cells, thereby preserving mitochondrial health. Blocking excessive Ca<sup>2</sup>⁺ entry confirmed the improvement in immune cell balance. Conversely, increased Ca<sup>2</sup>⁺ influx or disrupted mitochondrial function negated OCT's beneficial effects. Overall, OCT effectively ameliorates DPD by restoring the Treg/Th17 balance through alleviating store-operated Ca<sup>2+</sup> entry (SOCE) overactivation-induced mitochondrial dysfunction, suggesting it could be a promising approach for
{"title":"Maxacalcitol alleviates diabetes-associated periodontitis in male mice by restoring Treg/Th17 balance via SOCE-mediated mitochondrial dysfunction.","authors":"Xiaolin Li, Yujun Jiang, Minglei Zhang, Hongrui Liu, Minqi Li","doi":"10.1002/jper.70002","DOIUrl":"10.1002/jper.70002","url":null,"abstract":"<p><strong>Background: </strong>CD4<sup>+</sup> T lymphocytes play a central role in the pathogenesis of periodontitis, with the Treg/Th17 (regulatory T cell/T helper 17 cell) imbalance closely linked to diabetes-associated periodontitis (DPD). Maxacalcitol (OCT), an analog of active vitamin D, has therapeutic effects on diseases involving Treg/Th17 imbalance. This study aimed to determine whether OCT improved DPD by restoring the Treg/Th17 imbalance via store-operated Ca<sup>2+</sup> entry (SOCE)-mediated mitochondrial dysfunction.</p><p><strong>Methods: </strong>The DPD model was established in male C57BL/6 mice and treated with local injections or oral administration of OCT. Microcomputed tomography and flow cytometry were used to assess the alveolar bone, Treg/Th17 balance, and SOCE. Flow cytometry and transmission electron microscopy were applied to detect Treg/Th17 balance and mitochondrial function.</p><p><strong>Results: </strong>OCT attenuated alveolar bone loss and Treg/Th17 imbalance and enhanced the expressions of SOCE components in mice with DPD, with local injections showing more pronounced effects than oral administration. Furthermore, OCT restored the Treg/Th17 balance and improved mitochondrial dysfunction and overactivation of SOCE caused by lipopolysaccharides and high glucose. Additionally, SOCE inhibitors ameliorated mitochondrial abnormalities and Treg/Th17 imbalance under DPD conditions, whereas mitochondrial toxin and SOCE activators abolished the beneficial effects of OCT.</p><p><strong>Conclusions: </strong>OCT ameliorates Treg/Th17 imbalance via SOCE-mediated mitochondrial function, thereby effectively improving DPD.</p><p><strong>Plain language summary: </strong>Periodontitis, an inflammatory condition causing bone loss around teeth, is often more severe in individuals with diabetes due to immune system dysfunction. Specifically, diabetes-associated periodontitis (DPD) involves an imbalance between two types of immune cells: regulatory T cells (Treg), which control inflammation, and T helper 17 cells (Th17), which promote inflammation. This study explored how maxacalcitol (1α,25-dihydroxy-22-oxacalcitriol, OCT), a synthetic analog of active vitamin D3, treats DPD by correcting this immune cell imbalance. Using mouse models of DPD, we found that OCT significantly reduced bone loss and restored the balance between Treg and Th17 cells. Further investigation demonstrated that OCT functions by controlling calcium (Ca<sup>2</sup>⁺) entry into cells, thereby preserving mitochondrial health. Blocking excessive Ca<sup>2</sup>⁺ entry confirmed the improvement in immune cell balance. Conversely, increased Ca<sup>2</sup>⁺ influx or disrupted mitochondrial function negated OCT's beneficial effects. Overall, OCT effectively ameliorates DPD by restoring the Treg/Th17 balance through alleviating store-operated Ca<sup>2+</sup> entry (SOCE) overactivation-induced mitochondrial dysfunction, suggesting it could be a promising approach for","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}