Bone Reports最新文献

{"title":"Clinical features and treatment of hypophosphatemia and associated complications induced by Phosphaturic mesenchymal tumors: A case series of six patients","authors":"Guoqiang Lai ,&nbsp;Wangsheng Zuo ,&nbsp;Runmin Tang ,&nbsp;Zengbo Lu ,&nbsp;Dehai Shi","doi":"10.1016/j.bonr.2024.101822","DOIUrl":"10.1016/j.bonr.2024.101822","url":null,"abstract":"<div><div>Phosphaturic mesenchymal tumor (PMT) is a rare benign mesenchymal tumor characterized by excessive secretion of fibroblast growth factor 23 (FGF23), leading to phosphate loss and systemic osteomalacia. Despite recent progress in PMT research, no consensus on diagnosis and treatment guidelines has been established. This case series describes the clinical and pathological features of six pathologically confirmed PMT patients treated at the Third Affiliated Hospital of Sun Yat-sen University from 2010 to 2024, aiming to provide new insights for the management of this condition. The patients, consisting of three males and three females with an average age of 44 years and follow-up periods of 0.5 to 4.5 years, presented primarily with muscle pain and lower limb weakness. One patient experienced loose teeth, and two had palpable, painless masses. One case developed hyperphosphatemia, tertiary hyperparathyroidism, and renal impairment after prolonged phosphate supplementation. Tumor localization was achieved using 18F-FDG or 68Ga-DOTATATE Positron Emission Tomography-Computed Tomography(PET/CT) and MRI, followed by complete surgical resection. Pathological examination confirmed PMT, and postoperative recovery was marked by significant symptom relief and normalization of serum phosphate levels. Two patients experienced recurrence within three years but showed no further recurrence following repeat surgery by the last follow-up. The diagnosis of PMT is challenging and may take years, potentially leading to complications due to inadequate treatment. Complete tumor resection remains the primary treatment, generally resulting in a favorable prognosis; however, long-term monitoring is essential to detect potential recurrences and initiate timely interventions.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101822"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ano5Cys360Tyr mutation leads to bone dysfunction of gnathodiaphyseal dysplasia via disturbing Akt signaling","authors":"Hongyu Li,&nbsp;Shengnan Wang,&nbsp;Shuai Zhang,&nbsp;Rui Dong,&nbsp;Congcong Miao,&nbsp;Zhenchuan Tian,&nbsp;Ying Hu","doi":"10.1016/j.bonr.2025.101825","DOIUrl":"10.1016/j.bonr.2025.101825","url":null,"abstract":"<div><h3>Background</h3><div>Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant genetic disease characterized by osteosclerosis of the tubular bones and cemento-osseous lesions of the mandibles. <em>Anoctamin 5</em> (<em>ANO5</em>) is the pathogenic gene, however, the specific molecular mechanism of GDD remains unclear. Herein, a knockin (<em>Ano5</em>^{<em>KI/KI</em>}) mouse model expressing the human mutation p.Cys360Tyr was used to investigate the role of Akt signaling in enhanced osteogenesis and decreased osteoclastogenesis in GDD.</div></div><div><h3>Methods</h3><div>Bone marrow-derived macrophages (BMMs) and mouse calvarial osteoblasts (mCOBs) were isolated from homozygous <em>Ano5</em>^{<em>KI/KI</em>} mice and treated with SC79, a specific Akt activator. The differentiation and F-actin ring formation of osteoclasts were examined by TRAP and phalloidin staining, respectively. Osteoblast differentiation and mineralization were examined by ALP and alizarin red staining. The expression of bone remodeling-related factors was measured by qRT-PCR.</div></div><div><h3>Results</h3><div>Akt activation promoted the generation of TRAP-positive multinucleated osteoclasts and the formation of actin rings in <em>Ano5</em>^{<em>KI/KI</em>} BMMs cultures, accompanied by increased expression of <em>Nfatc1</em>, <em>Trap</em>, <em>Dc-stamp</em>, <em>Mmp9</em>, <em>Ctsk</em>, and <em>Atp6v0d2</em>. Additionally, <em>Ano5</em>^{<em>Cys360Tyr</em>} mutation down-regulated the Akt phosphorylation level in osteoblast. ALP activity and matrix mineralization capacity in <em>Ano5</em>^{<em>KI/KI</em>} osteoblast cultures were inhibited after SC79 stimulation, with reduced expression of <em>Runx2, Opn, Col1a1</em>, <em>and Ocn</em>.</div></div><div><h3>Conclusion</h3><div>Akt activation by SC79 stimulation can obviously rescue abnormal increased osteogenesis and decreased osteoclastogenesis in <em>Ano5</em>^{<em>KI/KI</em>} mouse model, which demonstrated that disturbed Akt signaling pathway may play a pivotal role in the pathogenesis of GDD, and an Akt activator is probable a therapeutic target for GDD.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101825"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel SGMS2 mutation associated with high bone mass; description of an affected family with recurrent fragility fractures","authors":"Shinjan Patra ,&nbsp;Sweekruti Jena ,&nbsp;Ketki Kedar ,&nbsp;Minal Pande ,&nbsp;Kishore K Katam ,&nbsp;Ashka Prajapti ,&nbsp;Udhaya Kotecha ,&nbsp;Parin Vyas","doi":"10.1016/j.bonr.2025.101833","DOIUrl":"10.1016/j.bonr.2025.101833","url":null,"abstract":"<div><div><em>SGMS2</em> mutation can present with childhood-onset low bone mass and recurrent fragility fractures. We report a 25-year-old man with a three-generation family history of recurrent fragility fractures and diffuse high bone mass. He was found to have a heterozygous frameshift variant c.1052_1074dup in the SGMS2 gene.</div><div>Our case highlights a novel genetic mutation in the <em>SGMS2</em> gene and reports the first family of <em>SGMS2</em> mutation with high bone mass.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101833"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterotopic ossification (HO) prophylaxis in total hip arthroplasty (THA): A systematic review of level I and level II evidence since 2000","authors":"Troy B. Puga ,&nbsp;McKenna W. Box ,&nbsp;Vincent M. Dieu ,&nbsp;Charles R. Marchese ,&nbsp;John T. Riehl","doi":"10.1016/j.bonr.2025.101828","DOIUrl":"10.1016/j.bonr.2025.101828","url":null,"abstract":"<div><h3>Introduction</h3><div>Heterotopic ossification (HO) is a somewhat common occurrence after total hip arthroplasty (THA), particularly with certain approaches. This complication can be detrimental to the success of the surgical outcome. Indomethacin and radiotherapy remain common treatment modalities; however, no true gold-standard treatment is universally agreed upon. This study aims to evaluate Level I and Level II evidence for treatment practices of HO prophylaxis since 2000.</div></div><div><h3>Methods</h3><div>To evaluate HO prophylaxis in total hip arthroplasty, a search was conducted across MEDLINE/Pubmed, Cochrane, and Embase databases using keywords and Medical Subject Heading (MeSH) terms. Titles and abstracts were screened for eligibility for inclusion criteria. Full texts were screened and included if they met eligibility criteria.</div></div><div><h3>Results</h3><div>HO chemical prophylaxis was more effective than no HO prophylaxis, except for aspirin. Multiple NSAIDs showed equivalence and better side effect profiles than indomethacin. No one superior NSAID was found, and numerous modalities showed efficacy. The most effective dosages of radiation therapy and combination therapy remain unclear. Additionally, both etidronate and salmon calcitonin showed benefit in preventing HO in one study each.</div></div><div><h3>Conclusion</h3><div>Radiation, NSAIDs, and combination therapy all showed efficacy as HO prophylaxis modalities. HO prophylaxis treatment and modalities should be guided upon patient and surgical factors such as surgical approach, side effects and tolerability of modalities, comorbidities, and available facility resources to optimize the prevention of HO.</div><div>Level of evidence: Level IV Therapeutic.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101828"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143158952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Cellularity as a predictive tool for mesenchymal stem cell concentration in bone marrow concentrates: Implications for regenerative medicine”","authors":"Klaus Werner Labarre,&nbsp;Peter Ansgar Grathwol,&nbsp;Gerald Zimmermann","doi":"10.1016/j.bonr.2024.101820","DOIUrl":"10.1016/j.bonr.2024.101820","url":null,"abstract":"<div><h3>Background</h3><div>Mesenchymal stem cells (MSCs) derived from bone marrow play an increasingly important role in regenerative medicine due to their capacity to promote tissue regeneration in various clinical contexts. Applications include the treatment of osteoarthritis, bone regeneration post-injury, and the management of conditions such as Crohn's disease, alopecia, and nervous system reconstruction. Accurate quantification of MSCs within Bone Marrow Concentrates (BMCs) is essential for ensuring the quality and efficacy of these cell therapy products in clinical settings.</div></div><div><h3>Objective</h3><div>This study aims to quantify the population of CD271⁺ and CD45⁻ cells in BMCs prepared using the method we have selected and to provide a basis for comparing these results with other BMC products. Additionally, we seek to determine whether the total cell count in BMCs can serve as a reliable indicator of MSC numbers and if cellularity (the number of cells per ml) can predict a higher percentage of MSCs within the population.</div></div><div><h3>Methods</h3><div>Bone Marrow Aspirates (BMA) were collected from 41 patients undergoing knee or hip arthroplasty. Aspirates were processed using density gradient centrifugation and positive selection of CD271⁺ cells. Flow cytometry was applied to analyze cell subsets, and cell counts were determined with a NucleoCounter. The relationships between BMA cellularity (total cells per ml), MSC concentration (MSC count per ml), and MSC percentage (the proportion of MSCs within the total cell population) were assessed.</div></div><div><h3>Results</h3><div>The mean percentage of CD271⁺ CD45⁻ cells in bone marrow samples was 0.03 % (SD 0.03 %). Cellularity varied significantly among samples, with a mean of 6 million cells/ml (SD 8.7 million cells/ml). A strong correlation was observed between BMC cellularity and MSC concentration (<em>p</em> &lt; 0.05), although no correlation was found between cellularity and the MSC percentage.</div></div><div><h3>Conclusion</h3><div>Despite high variability in cellularity, the concentration of MSCs correlated strongly with BMC cellularity, suggesting that total cell counts can be used to estimate MSC numbers in BMCs. However, cellularity is not an indicator of a particularly high MSC content. This study supports the use of cell counts as a measure for estimating MSC concentration in BMCs. Future research should focus on establishing direct comparisons with other BMC products and exploring factors influencing cellularity and MSC percentages to enhance BMC quality for clinical applications.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"24 ","pages":"Article 101820"},"PeriodicalIF":2.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of ultrasound imaging in monitoring fracture healing in rat femur: Comparison with other imaging modalities","authors":"Satoshi Inoue ,&nbsp;Michinori Mori ,&nbsp;Masaya Yasui ,&nbsp;Miwako Matsuki-Fukushima ,&nbsp;Kentaro Yoshimura ,&nbsp;Naoko Nonaka","doi":"10.1016/j.bonr.2024.101807","DOIUrl":"10.1016/j.bonr.2024.101807","url":null,"abstract":"<div><h3>Objective</h3><div>Fractures are common injuries and various imaging modalities are employed to diagnose and monitor bone union. However, the follow-up of fracture healing using ultrasound imaging (US) remains a topic of debate. In this study, we analyzed of fracture healing process and compared US and radiological analyses with histological analyses to clarify the characteristics and limitations of each modality.</div></div><div><h3>Methods</h3><div>An osteotomy model was created using the femur of Wistar rats, and US, radiological (radiography and micro-computed tomography (micro-CT)), and histological analyses were performed. Radiological assessments were conducted for the evaluation of calcified tissue. The gap between the bony callus and cartilaginous callus was measured.</div></div><div><h3>Results</h3><div>US effectively captured changes on the fracture surface, potentially reflecting the early healing processes. Both US and radiographic findings showed strong correlation in terms of the decrease in the bony callus gap. US was unable to distinguish cartilaginous callus from the surrounding soft tissue. During the remodeling stage, micro-CT offered a detailed assessment of the internal fracture surface, whereas US was limited to evaluating the outer bone surface and lacked accuracy in visualizing the entire fracture site. Radiography provided a general overview of the fractures. The decrease in the bony callus gap measured using US correlated with the reduction in cartilaginous callus observed histologically.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that US could be a valuable tool for evaluating fracture healing. Combining fracture management with US and radiological examinations may provide a more accurate assessment of healing progress.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"23 ","pages":"Article 101807"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352187224000743/pdfft?md5=b4602ad835bfbf30c300979e46abe843&pid=1-s2.0-S2352187224000743-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying the best reference gene for RT-qPCR analyses of the three-dimensional osteogenic differentiation of human induced pluripotent stem cells","authors":"Masakazu Okamoto ,&nbsp;Yusuke Inagaki ,&nbsp;Kensuke Okamura ,&nbsp;Yoshinobu Uchihara ,&nbsp;Kenichiro Saito ,&nbsp;Akihito Kawai ,&nbsp;Munehiro Ogawa ,&nbsp;Akira Kido ,&nbsp;Eiichiro Mori ,&nbsp;Yasuhito Tanaka","doi":"10.1016/j.bonr.2024.101816","DOIUrl":"10.1016/j.bonr.2024.101816","url":null,"abstract":"<div><div>Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is an essential tool for gene expression analysis; choosing appropriate reference genes for normalization is crucial to ensure data reliability. However, most studies on osteogenic differentiation have had limited success in identifying optimal reference genes. To the best of our knowledge, no optimal reference genes in three-dimensional (3D) osteogenic differentiation culture experiments using human induced pluripotent stem cells (hiPSCs) have been identified. In this study, we aimed to identify stable reference genes that could be used for normalization in gene expression analyses during the 3D osteogenic differentiation of hiPSCs using an atelocollagen sponge as a scaffold. Four algorithms—ΔCt, BestKeeper, NormFinder, and geNorm—were used to evaluate the stability of 14 candidate reference genes. Genes encoding TATA box-binding protein, hypoxanthine phosphoribosyltransferase 1, and 14–3-3 protein zeta polypeptide were identified as the most stable reference genes. In comparison, conventionally used reference genes (beta-2 microglobulin and beta-actin genes) ranked among those with low stability. We also demonstrated the successful 3D osteogenic differentiation of hiPSCs on atelocollagen sponge. Our findings provide valuable insights for reference gene selection and bone tissue regeneration from hiPSCs, which could improve the treatment prospects for bone defects and other similar conditions in regenerative medicine.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"23 ","pages":"Article 101816"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142703388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones","authors":"Anne Briolay ,&nbsp;François Duboeuf ,&nbsp;Séverine Delplace ,&nbsp;Leyre Brizuela ,&nbsp;Olivier Peyruchaud ,&nbsp;David Magne ,&nbsp;Carole Bougault","doi":"10.1016/j.bonr.2024.101810","DOIUrl":"10.1016/j.bonr.2024.101810","url":null,"abstract":"<div><div>Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions (<em>n</em> = 20 per group). Free access to activity wheels resulted in a running exercise of 5.5 ± 0.8 km/day at 14.5 ± 0.5 m/min. Serum levels of alkaline phosphatase, IL-6, IL-8/Kc, IL-17a, and TNF-α were measured. No change in systemic inflammation was detected. The bone architecture of the femur and the calcaneus was unchanged, as revealed by μCT and histology of the enthesis of the Achilles tendon. mRNAs were extracted from femurs, tibias, and ankle joints before RT-qPCR analysis. The expression of the mechanosensitive genes <em>Sclerostin</em> (<em>Sost</em>) and <em>Periostin</em> (<em>Postn</em>) was not impacted by the exercise in long bones. Oppositely, <em>Sost</em> and <em>Postn</em> levels were modulated by exercise in joints, and osteogenic markers (<em>Col10a1</em>, <em>Runx2</em>, <em>Osx</em>, and <em>Dmp1</em>) were downregulated in the exercise group. In addition, the tenogenic markers <em>Scx</em>, <em>Mkx</em>, and <em>Tnmd</em> were upregulated by exercise. Thus, voluntary exercise affected the phenotype of joint cells without impacting long bones. As gene expression of <em>Bmp2</em>, <em>Bmp4</em>, and <em>Id1</em> was also reduced in these cells, an off-regulation of BMP signaling could be partly responsible for their mechanosensitive response. Running exercise seemed to preserve the tendon from its progressive ossification, as seen in numerous enthesopathies. This study paves the way to future experiments for investigating the effects of mechanical stimulation in various mouse models.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"23 ","pages":"Article 101810"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvements with burosumab treatment in an early access programme for adults with X-linked hypophosphataemia: A case series of three patients","authors":"Julia Day ,&nbsp;Chandrin Jayatilleke ,&nbsp;Matthew Roy","doi":"10.1016/j.bonr.2024.101814","DOIUrl":"10.1016/j.bonr.2024.101814","url":null,"abstract":"<div><div>X-linked hypophosphataemia (XLH) is a life-long phosphate-wasting disorder that causes skeletal deformities, pain, stiffness, and fatigue and impairs quality of life. Burosumab was approved for use in adults in 2020. We describe three adults with persistent XLH symptoms who received burosumab treatment in a real-world setting. Patients report improvements in pain, mobility, physical function, energy, fatigue, and mental wellbeing through patient-reported outcome measures, enriched with further detail from written testimonials.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"23 ","pages":"Article 101814"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway","authors":"Mohamed Awad ,&nbsp;Elizabeth Taylor-Diaz ,&nbsp;Amany Tawfik ,&nbsp;Khaled Hussein ,&nbsp;Ahmed Elmansi ,&nbsp;Mahmoud Elashiry ,&nbsp;Ranya Elsayed ,&nbsp;Linah Shahoumi ,&nbsp;James Borke ,&nbsp;William Hill ,&nbsp;Fanglong Dong ,&nbsp;Mohammed E. Elsalanty","doi":"10.1016/j.bonr.2024.101812","DOIUrl":"10.1016/j.bonr.2024.101812","url":null,"abstract":"<div><h3>Introduction</h3><div>In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ).</div></div><div><h3>Methods</h3><div>The effect of zoledronate on the expression of SDF1 was tested in pre-osteoclasts (POC) in vitro. Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry.</div></div><div><h3>Results</h3><div>SDF-1 mRNA expression decreased in Zol-treated POCs (<em>p</em> = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12⁺ (SDF-1α) expressing POCs with Zol treatment (<em>p</em> = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs (<em>p</em> = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol (<em>p</em> = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration (<em>p</em> = 0.0012), and tube formation (<em>p</em> &lt; 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31⁺ HUVECs in Alveolar bone of Zol-treated rats (<em>p</em> = 0.0071), confirmed by significantly lower percentage of blood vessel volume (<em>p</em> = 0.026), and marginally lower vessel number (<em>p</em> = 0.062) in the alveolar bone.</div></div><div><h3>Conclusion</h3><div>Pre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. Disruption of this process may be a predisposing factor to osteonecrosis.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"23 ","pages":"Article 101812"},"PeriodicalIF":2.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}