Bone & Joint Research最新文献

{"title":"Increasing reaming depth enhances implant stability while minimizing bone strain.","authors":"Monil Karia, Ruben Doyle, Adam Reynolds, Jonathan Jeffers, Justin Cobb","doi":"10.1302/2046-3758.146.BJR-2024-0118.R3","DOIUrl":"https://doi.org/10.1302/2046-3758.146.BJR-2024-0118.R3","url":null,"abstract":"<p><strong>Aims: </strong>Increasing the interference fit of the acetabular component can increase primary stability, but it introduces excessive periacetabular strain during impaction, which can lead to fractures. An optimal outcome following cementless acetabular component impaction is maximal primary implant stability with minimal periacetabular bone strain. The aim of this study was to investigate whether a simple modification to a surgeon's reaming technique can achieve this desirable outcome.</p><p><strong>Methods: </strong>A custom drop rig simulated impaction strikes, seating acetabular components of either 1 mm or 2 mm interference fit into synthetic sawbones with cavities reamed to either a true hemisphere or a hemisphere with an enhanced reaming depth of 2 mm or 4 mm. Synthetic bone strain was recorded using strain gauges, and push-out tests were conducted to assess implant stability. Polar gaps were measured using optimal trackers.</p><p><strong>Results: </strong>Compared to a true hemispherical cavity, enhancing the reaming depth significantly increased the primary stability of the implant (p < 0.001) while reducing both the periacetabular strain and strain deterioration for both 1 mm and 2 mm interference fit components. A 4 mm reaming depth enhanced the primary stability of 1 mm press-fit components to a level almost equivalent to a 2 mm press-fit, albeit reducing strain to the bone. Enhancing reaming depth did not significantly affect polar gap.</p><p><strong>Conclusion: </strong>Enhancing cavity reaming depth is a simple technique to increase the implant primary stability of press-fit uncemented acetabular components, while avoiding any excess in periacetabular strain and the associated fracture risk.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 6","pages":"551-559"},"PeriodicalIF":4.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324461","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}

{"title":"Single-cell transcriptomics analysis of the healing process of ligament rupture.","authors":"Haibo Zhao, Jianbao Gong, Tengbo Yu, Yingze Zhang","doi":"10.1302/2046-3758.146.BJR-2024-0307.R3","DOIUrl":"10.1302/2046-3758.146.BJR-2024-0307.R3","url":null,"abstract":"<p><strong>Aims: </strong>The repair process of ligament ruptures is a complex phenomenon involving three stages: early, repair, and remodelling. This study aimed to investigate the cellular and genetic aspects related to the repair and healing of ligament ruptures using single-cell RNA sequencing (scRNA-seq) on anterior cruciate ligament (ACL) tissues.</p><p><strong>Methods: </strong>A comprehensive examination was conducted on ACL tissues from three healthy individuals and three patients with ligament ruptures at different timepoints (one week, three weeks, and six months post-injury). A deep gene expression analysis was performed on 83,195 cells obtained from the six cases, and immunohistochemistry techniques were used to identify cell types.</p><p><strong>Results: </strong>In this study, tenocytes and fibroblasts in ligament tissues were distinctly identified for the first time. Moreover, a total of ten cell populations were discovered in ACL tissues, comprising tenocytes, fibroblasts, macrophages, stromal cells, T cells, endothelial cells, B cells, epithelial cells, chondrocytes, and monocytes. Further analysis of the tenocyte populations revealed ten distinct subtypes, highlighting the diversity of tenocytes in human ACL tissues.</p><p><strong>Conclusion: </strong>The identification of multiple specialized tenocyte populations in human ACL tissues sheds light on potential avenues for advancing research in cell therapy for ligament injuries. These findings provide valuable insights into the cellular components involved in the repair and healing processes of ligament ruptures, paving the way for future investigations in this field.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 6","pages":"539-550"},"PeriodicalIF":4.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal- and concentration-dependent effects of transforming growth factor-beta 1 (TGF-β1) in primary human knee fibroblasts.","authors":"Oliver B Dilger, Mason F Carstens, Daphne J Garrett, Daniel J Berry, Joaquin Sanchez-Sotelo, Mark E Morrey, Roman Thaler, Amel Dudakovic, Matthew P Abdel","doi":"10.1302/2046-3758.146.BJR-2024-0387.R3","DOIUrl":"10.1302/2046-3758.146.BJR-2024-0387.R3","url":null,"abstract":"<p><strong>Aims: </strong>To characterize the effects of varying experimental parameters of transforming growth factor-beta 1 (TGF-β1) in primary knee fibroblasts as an in vitro model of arthrofibrosis.</p><p><strong>Methods: </strong>Primary knee fibroblasts were isolated from one patient undergoing primary total knee arthroplasty (TKA) and one patient undergoing revision TKA for arthrofibrosis, respectively. Fibroblasts were stimulated with varying concentrations and durations of the pro-fibrotic cytokine TGF-β1. Picrosirius red staining (PSR) was conducted to assess collagen deposition, and real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine cellular gene expression levels. A collagen gel contraction assay was used to assess TGF-β1-induced fibroblast contraction.</p><p><strong>Results: </strong>In our experiments, TGF-β1-mediated collagen deposition was consistent across a vast concentration range (0.5 to 40 ng/ml). While α-smooth muscle actin (ACTA2) protein levels and SMAD2 phosphorylation were induced by low concentrations (1 ng/ml), robust <i>ACTA2</i> transcription required higher concentrations (5 ng/ml) of TGF-β1. Evaluation of TGF-β1-mediated cell and cytoskeletal contractility shows that in the measured fibroblasts, this process occurs within three hours following TGF-β1 administration. Of note, TGF-β1-differentiated myofibroblasts exhibited greater contractile properties than naïve fibroblasts in the presence of TGF-β1.</p><p><strong>Conclusion: </strong>Taken together, this study elucidates key TGF-β1 experimental parameters that will inform the development and interpretation of in vitro models of arthrofibrosis.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 6","pages":"527-538"},"PeriodicalIF":4.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hederagenin promotes SIRT6 to attenuate epidural scar formation by aggravating PRMT1 deacetylation.","authors":"Xiao-Chen Fan, Jue Wang","doi":"10.1302/2046-3758.146.BJR-2024-0287.R2","DOIUrl":"10.1302/2046-3758.146.BJR-2024-0287.R2","url":null,"abstract":"<p><strong>Aims: </strong>The formation of a postoperative epidural scar induced by epidural fibrosis is the main reason for recurrence of lumbar disc herniation after laminectomy. Hederagenin (HE) has been found to be widely present in various medicinal plants and has various pharmacological functions. This study aimed to investigate the effect and regulatory mechanism of HE on epidural scar formation.</p><p><strong>Methods: </strong>Transforming growth factor beta 1 (TGF-β1)-stimulated epidural scar fibroblasts were used as an in vitro cell model. Based on that, HE treatment was carried out along with sirtuin-6 (<i>SIRT6)</i> silence or protein arginine N-methyltransferase 1 (<i>PRMT1</i>) overexpression. The interaction between SIRT6 and PRMT1 was evaluated by pulldown and co-immunoprecipitation (CoIP) assays. Then, cell proliferation, apoptosis, and fibrosis were measured by Cell Counting Kit (CCK)-8, flow cytometry, and western blotting. Moreover, the effects of receptor activator of nuclear factor-κB ligand (RANKL) supplementation and endoplasmic reticulum (ER) stress were also evaluated by supplementing recombinant protein and specific inhibitor or activator.</p><p><strong>Results: </strong>HE depressed cell proliferation and fibrosis, while inducing apoptosis of epidural fibroblasts. Meanwhile, HE promoted <i>SIRT6</i> expression which suppressed PRMT1 acetylation and protein stability. Additionally, HE induced ER stress and upregulated RANKL in epidural fibroblasts via mediating <i>SIRT6</i>/<i>PRMT1</i> axis.</p><p><strong>Conclusion: </strong>Generally, the therapeutic role of HE treatment on epidural scar formation was exerted by regulating <i>SIRT6</i>/<i>PRMT1</i> axis-mediated ER stress and RANKL pathway. This study provides evidence of a novel therapeutic measure for epidural scar formation.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 6","pages":"516-526"},"PeriodicalIF":4.7,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-year follow-up of 20 patients undergoing the Latarjet procedure : a biomechanical study during an apprehension-relocation test measured with radiostereometry.","authors":"Josephine Olsen Kipp, Emil Toft Petersen, Maiken Stilling, Sepp De Raedt, Anna Zejden, Rikke Jellesen Åberg, Thomas Falstie-Jensen, Theis Muncholm Thillemann","doi":"10.1302/2046-3758.146.BJR-2024-0533.R1","DOIUrl":"10.1302/2046-3758.146.BJR-2024-0533.R1","url":null,"abstract":"<p><strong>Aims: </strong>The Latarjet procedure is the treatment of choice for patients who have recurrent anterior shoulder instability with glenoid bone loss. However, the stabilizing effect of the Latarjet procedure in patients is sparsely described. The aim of this study was to evaluate the glenohumeral joint (GHJ) kinematics during an apprehension-relocation test in patients with anterior shoulder instability before and after their Latarjet procedure, and in comparison with their contralateral healthy shoulder.</p><p><strong>Methods: </strong>A total of 20 patients scheduled for the Latarjet procedure were enrolled. The patients were examined preoperatively with bilateral radiostereometric analysis (RSA) and one year after surgery on the operated shoulder with an apprehension-relocation test. Bone models were obtained from CT scans and aligned with the RSA images. The GHJ kinematics was evaluated with two methods: the humeral head centre location relative to the glenoid centre, and the GHJ contact point relative to the glenoid centre.</p><p><strong>Results: </strong>No difference in GHJ kinematics was found between the healthy and the postoperative GHJ. Compared with the preoperative injured shoulder, the postoperative mean (95% CI) humeral head centre was 0.8 mm (0.1 to 1.4) more superior and 0.7 mm (-0.1. to 1.4) more posterior during the apprehension test, and 0.5 mm (0.0 to 1.1) more posterior during the relocation test. The postoperative contact point was posterior to the coracoid bone block and 0.9 mm (-0.2 to 2.0) more posterior than in the preoperative injured shoulder during the apprehension test. The articulating area of the coracoid bone block was decreased by 63.9% (75.5 to 114.6) one year after surgery.</p><p><strong>Conclusion: </strong>The Latarjet procedure restored the humeral head centre location posterior and superior, and the contact point posterior, to the coracoid bone block. This suggests that the stabilizing effect of the GHJ following the Latarjet procedure is primarily due to the conjoined tendon rather than the coracoid bone block itself.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 6","pages":"506-515"},"PeriodicalIF":4.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Objectively measured activity behaviours using the ActivPAL accelerometer following robotic and manually performed total knee arthroplasty : a feasibility study from a randomized controlled trial (ROAM study).","authors":"Nick D Clement, Bola Ajekigbe, Jayasree Ramaskandhan, Steven Galloway, Karen Smith, David J Weir, David J Deehan","doi":"10.1302/2046-3758.146.BJR-2024-0239.R1","DOIUrl":"10.1302/2046-3758.146.BJR-2024-0239.R1","url":null,"abstract":"<p><strong>Aims: </strong>To assess whether it was feasible to objectively measure activity behaviour between robotic arm-assisted (raTKA) and manually performed (mTKA) total knee arthroplasty using the ActivPAL accelerometer.</p><p><strong>Methods: </strong>A randomized controlled trial was undertaken and a subgroup of 40 patients underwent physical activity assessment. Patients were randomized to either mTKA (n = 18) or raTKA (n = 22). Preoperative (baseline) and 12-month postoperative physical activity assessment were undertaken using the ActivPAL accelerometer in addition to patient-reported outcome measures (PROMs): Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Forgotten Joint Score (FJS), EuroQol five-dimension questionnaire (EQ-5D), and EuroQol visual analogue scale (EQ-VAS). At 12 months, 15 patients in the raTKA group and nine in the mTKA group had paired ActivPAL data for analysis. Of the 16 patients without data, four withdrew, four were not provided with the ActivPAL due to logistical reasons, one failed to return the ActivPAL, one was allergic to the ActivPAL patch, and six failed to record or the data were corrupt.</p><p><strong>Results: </strong>There were no significant differences in the improvement in standing time (mean difference (MD) 1.6, p = 0.924), step number (MD 62.0, p = 0.970), sitting time (16.3, p = 0.777), number of sit-to-stand transitions (MD 16.3, p = 0.579), or activity scores (MD 0.0, p = 0.977) between the groups. However, the raTKA had a clinically meaningful and significantly (MD 19.8, 95% CI 0.8 to 38.8; p = 0.041) greater improvement in knee-specific pain according to the WOMAC pain score. There were no other statistically significant (p ≥ 0.113) differences between the other PROMs. There were no significant (p ≥ 0.144) correlations between changes in measures of physical activity functional assessments.</p><p><strong>Conclusion: </strong>Objectively assessed physical activity was logistically difficult due to patient and data loss. There were no differences in activity with small effect sizes (≤ 0.2) between the raTKA and mTKA groups, despite differences in subjective knee pain. Improvement in subjective PROMs did not correlate with objectively measured physical activity, and the two seemed to be independent of one another.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 6","pages":"495-505"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction heating combined with antibiotics or SAAP-148 effectively reduces biofilm-embedded Staphylococcus aureus on a fracture-related implant mimic.","authors":"Marielle Verheul, Anne A Wagenmakers, Rob G H H Nelissen, Peter H Nibbering, Bart G Pijls","doi":"10.1302/2046-3758.145.BJR-2024-0341.R1","DOIUrl":"10.1302/2046-3758.145.BJR-2024-0341.R1","url":null,"abstract":"<p><strong>Aims: </strong>Fracture-related infections and the associated treatment failure burden our society and healthcare system significantly. As an alternative approach, we investigated the effect of non-contact induction heating (NCIH) against <i>Staphylococcus aureus</i> within mature biofilms. In addition, we assessed the ability of antibiotics, the antimicrobial peptide SAAP-148, and bacteriophage (phage) ISP to enhance the efficacy of NCIH, thereby allowing the use of lower temperatures during NCIH.</p><p><strong>Methods: </strong>Clinical isolates of methicillin-resistant and methicillin-sensitive <i>S. aureus</i> (methicillin-resistant <i>S. aureus</i> (MRSA), methicillin-sensitive <i>S. aureus</i> (MSSA)) were cultured for seven days on Ti-6Al-7Nb (mimicking fracture plates) discs to obtain mature biofilms. Biofilms were exposed to 60°C to 80°C NCIH. In addition, biofilms were sequentially exposed to 60°C to 70°C NCIH and rifampicin/ciprofloxacin, SAAP-148, or phage ISP. Biofilm-embedded bacteria were harvested by sonication to determine the bacterial load and visualized by confocal microscopy (LIVE/DEAD).</p><p><strong>Results: </strong>NCIH to 60°C, 70°C, and 80°C reduced biofilm-embedded MRSA and MSSA by 2.3-log, 4.9-log, 5.5-log, and 1.1-log, 3.4-log, and 6.6-log CFU/ml, respectively. LIVE/DEAD staining revealed NCIH-induced bacterial cell death throughout the biofilm layers. The sequential combination of rifampicin/ciprofloxacin at 10 µg/ml and 1,280 µg/ml (MRSA) or 156 µg/l and 64 µg/ml (MSSA) and 70°C NCIH synergistically reduced biofilm-embedded bacteria by 2.7-log and 3.7-log CFU/ml, respectively, while the alternating exposure order reduced bacterial counts by -0.1 and 1.7-log CFU/ml. SAAP-148 at 51.2 µM followed by 70°C NCIH further diminished biofilm-embedded MRSA and MSSA by 2.3-log and 1.5-log CFU/ml, respectively. No significant reductions were observed for NCIH combined with phage ISP compared to these treatments alone.</p><p><strong>Conclusion: </strong>NCIH effectively reduced biofilm-embedded <i>S. aureus</i> on Ti-6Al-7Nb in a heat-dependent fashion. Rifampicin/ciprofloxacin and SAAP-148, but not phage ISP, enhanced the efficacy of NCIH. Antibiotic exposure at suboptimal concentrations followed by NCIH was more effective than vice versa, suggesting that the application of this approach might be most suitable in clinical situations where antibiotic treatment has already started.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 5","pages":"485-494"},"PeriodicalIF":4.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem introducer designs and surgical technique play a significant role in achieving the optimal implant-cement interface.","authors":"Bernard H van Duren, Kevin Ilo, Sophie Walker, Mark Higgins, Benjamin V Bloch, Andrew R Manktelow, Hemant G Pandit","doi":"10.1302/2046-3758.145.BJR-2024-0273.R1","DOIUrl":"10.1302/2046-3758.145.BJR-2024-0273.R1","url":null,"abstract":"<p><strong>Aims: </strong>Periprosthetic fracture is a major contributor to reoperation with polished taper slip (PTS) cemented stems, which is the most used fixation technique in many countries. A clear cause for this has yet to be established. A significant variation exists between PTS stem designs, associated fractured rates among them, and the design of introducers used. Achieving a conforming implant-cement interface (ICI) is crucial to ensure optimal function of PTS implants. Movement of the stem within the setting cement during surgery should be uniplanar, and should not be associated with any unplanned deviations. This is in part controlled by the stem introducer design, which potentially contributes to excess movement and ICI compromise. The aim of this study was to assess movement when using different introducer designs.</p><p><strong>Methods: </strong>We compared four stem introducer designs used with two commonly used PTS stems. The stems were mounted using a silicone rubber compound to simulate setting cement at different timepoints (early = soft, late = hard). The stem tips were left clear, and an inertial measurement unit attached to measure acceleration, angular velocity, and rotation. Participating surgeons (n = 16) were asked to maintain stem position for ten seconds before releasing the introducer.</p><p><strong>Results: </strong>Simulation of soft cement conditions showed a mean root mean square (RMS) value ranging from 0.10 g to 0.30 g for acceleration, 12.75°/s to 67.94°/s for angular velocity, and 2.02° to 6.03° for rotation with significant differences noted between different stem introducers. Simulation of later insertion during the curing process (hard) showed a similar pattern, with a lower overall range of motion.</p><p><strong>Conclusion: </strong>Our results showed that introducer design had a significant impact on stem movement within the setting cement. Furthermore, its removal earlier in the setting reaction resulted in increased movement. These findings highlight the importance of instrument design and correct technique in achieving the optimal ICI.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 5","pages":"477-484"},"PeriodicalIF":4.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCR4 is a response gene for parathyroid hormone which affects osteoblast and osteoclast function in vitro.","authors":"Beatriz Larraz-Prieto, Louise Hjorth Lind, Jacob Bastholm Olesen, Asim Azfer, Morten Svarer Hansen, Morten Frost, Abbas Jafari, Stuart H Ralston, Kent Søe, Nerea Alonso","doi":"10.1302/2046-3758.145.BJR-2024-0167.R1","DOIUrl":"10.1302/2046-3758.145.BJR-2024-0167.R1","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the role of CXCR4 in response to teriparatide (TPTD) treatment in osteoblasts and osteoclasts.</p><p><strong>Methods: </strong>Primary murine and human osteoblasts and osteoclasts, MC3T3 cell lines, and hMSC-TERT4 cell lines were treated with TPTD and/or AMD3100, a pharmacological inhibitor of CXCR4. Changes in gene expression, osteoblast viability, mobility, mineralization capacity, and alkaline phosphatase activity were investigated. Osteoclastogenesis and cell fusion were also assessed in response to both treatments.</p><p><strong>Results: </strong>TPTD increased messenger RNA levels of <i>CXCR4</i> in all stages of both murine and human osteoblast differentiation. Mineralization analysis showed that CXCR4 was involved in bone matrix formation in response to TPTD. Alkaline phosphatase activity was also impaired by CXCR4 inhibition at early stages of osteoblast differentiation, while it was promoted at late stages, suggesting that CXCR4 could produce a delay in osteoblast maturation. Moreover, we also found a direct activation of osteoclastogenesis after TPTD treatment in murine and human osteoclasts. This process seems to involve CXCR4 activity, since AMD3100-induced CXCR4 inhibition led to a reduction in both murine and human osteoclastogenesis. This process, however, could not be prevented by TPTD treatment.</p><p><strong>Conclusion: </strong>Our results suggest that <i>CXCR4</i> is a responsive gene to TPTD treatment, involved in the regulation of osteoblast and osteoclast generation and function. Further in vivo studies are required to confirm this role, and to determine whether pharmacological strategies targeting CXCR4 could potentially improve the treatment outcome for osteoporotic patients.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 5","pages":"463-476"},"PeriodicalIF":4.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of elevated sclerostin levels on bone resorption : unravelling structural changes and mineral metabolism disruption.","authors":"María Encarnacion Rodríguez-Ortiz, Juan Miguel Díaz-Tocados, Ana Isabel Torralbo, Karen Valdés-Díaz, Antonio Rivas-Domínguez, Fátima Guerrero, Irene Reina-Alfonso, Manuel Naves-Díaz, Cristina Alonso-Montes, Cristian Rodelo-Haad, Mariano Rodríguez, Juan Rafael Muñoz-Castañeda, Rodrigo López-Baltanas, Daniel Jurado-Montoya, Javier Barba, Andrés Carmona, Teresa Obrero, Julio M Martínez-Moreno, Raquel M García-Sáez, M Victoria Pendón-Ruiz de Mier","doi":"10.1302/2046-3758.145.BJR-2024-0227.R1","DOIUrl":"10.1302/2046-3758.145.BJR-2024-0227.R1","url":null,"abstract":"<p><strong>Aims: </strong>The physiological function of sclerostin remains unknown. Sclerostin is synthesized by osteocytes and operates by inhibiting the Wnt/β-catenin pathway. Similarly, it is well established that low levels of sclerostin lead to enhanced bone formation and reduced calciuria, and that high levels of sclerostin are associated with osteoporosis.</p><p><strong>Methods: </strong>The impact of high levels of recombinant sclerostin on bone and mineral metabolism parameters was analyzed in this study. In male healthy rats, the effects of three elevated doses of sclerostin over a 14-day period were studied, involving bone histomorphometry, micro-CT (μCT), immunohistochemistry, and analysis of mineral metabolism parameters.</p><p><strong>Results: </strong>Although there was increased bone formation, high doses of sclerostin led to a higher reduction in trabecular bone volume due to a significant increase in bone resorption through the direct activation of osteoclastogenesis. In vitro, sclerostin promoted the differentiation of bone marrow stem cells into osteoclasts. Bone resorption, as measured by tartrate-resistant acid phosphatase (TRAP) activity, was excessive in trabecular, cortical, and subchondral bone. Similarly, high doses of sclerostin increased the number of hypertrophic chondrocytes, consequently expanding the growth plate area. At the cortical level, positive TRAP staining could be observed, suggestive of osteocytic osteolysis and trabecularization of cortical bone. The increased bone resorption resulted in a substantial rise in the urinary excretion of phosphorus and calcium, accompanied by elevated levels of FGF23 and a significant decrease in parathyroid hormone (PTH).</p><p><strong>Conclusion: </strong>These findings suggest that elevated levels of sclerostin promote bone resorption through the activation of osteoclasts and the generation of osteocytic osteolysis, resulting in increased calciuria, phosphaturia, and changes in mineral metabolism.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 5","pages":"448-462"},"PeriodicalIF":4.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}