JOR Spine最新文献

{"title":"Comparative Analysis of Dual-miRNA Mediated Stimulation of Nucleus Pulposus and Bone Marrow Derived Stem Cells for Intervertebral Disc Repair","authors":"Tara Ní Néill,&nbsp;Niamh Wilson,&nbsp;Jake McDonnell,&nbsp;Fergal J. O'Brien,&nbsp;Caroline M. Curtin,&nbsp;James E. Dixon,&nbsp;Pieter A. J. Brama,&nbsp;Conor T. Buckley","doi":"10.1002/jsp2.70198","DOIUrl":"https://doi.org/10.1002/jsp2.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is the primary cause of low back pain (LBP). Disease progression is characterized by a shift in extracellular matrix homeostasis towards degradation over regeneration, a process that is a key target of emerging therapeutic strategies. Our laboratory has previously identified the dual delivery of FLR-miRNA-149-5p mimic and 221-3p inhibitor as being beneficial in generating an anti-catabolic regenerative niche. Cell therapies have likewise demonstrated potential, though the most suitable cell source has been debated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this study, we explored the stimulation of nucleus pulposus and bone marrow derived stem cells with our therapeutic miRNA pair, with the aim of identifying the most suitable cell population for delivery to the IVD. Culture systems of increasing complexity ranging from monolayer to ex vivo organ culture were employed using caprine cells and IVD organs due to their physiological relevance to humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrated the maintenance of our previously reported anti-catabolic niche, with significant downregulation of matrix degrading factors, ADAMTS5 and MMP13 and pro-inflammatory cytokines, TNF and IL-1β. Furthermore, delivery of dual-miRNA stimulated nucleus pulposus cells in an organ culture model of mild IVD degeneration significantly upregulated the matrix markers, SOX9 and aggrecan. However, this matrix response was not identified in dual-miRNA-bone marrow derived stem cells delivered to goat IVD organs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, these findings highlight the potential of nucleus pulposus cells as a regenerative cell source when combined with FLR-miRNA-149-5p mimic and 221-3p inhibitor for the treatment of LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Dual-miRNA Mediated Stimulation of Nucleus Pulposus and Bone Marrow Derived Stem Cells for Intervertebral Disc Repair","authors":"Tara Ní Néill,&nbsp;Niamh Wilson,&nbsp;Jake McDonnell,&nbsp;Fergal J. O'Brien,&nbsp;Caroline M. Curtin,&nbsp;James E. Dixon,&nbsp;Pieter A. J. Brama,&nbsp;Conor T. Buckley","doi":"10.1002/jsp2.70198","DOIUrl":"https://doi.org/10.1002/jsp2.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc (IVD) degeneration is the primary cause of low back pain (LBP). Disease progression is characterized by a shift in extracellular matrix homeostasis towards degradation over regeneration, a process that is a key target of emerging therapeutic strategies. Our laboratory has previously identified the dual delivery of FLR-miRNA-149-5p mimic and 221-3p inhibitor as being beneficial in generating an anti-catabolic regenerative niche. Cell therapies have likewise demonstrated potential, though the most suitable cell source has been debated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In this study, we explored the stimulation of nucleus pulposus and bone marrow derived stem cells with our therapeutic miRNA pair, with the aim of identifying the most suitable cell population for delivery to the IVD. Culture systems of increasing complexity ranging from monolayer to ex vivo organ culture were employed using caprine cells and IVD organs due to their physiological relevance to humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrated the maintenance of our previously reported anti-catabolic niche, with significant downregulation of matrix degrading factors, ADAMTS5 and MMP13 and pro-inflammatory cytokines, TNF and IL-1β. Furthermore, delivery of dual-miRNA stimulated nucleus pulposus cells in an organ culture model of mild IVD degeneration significantly upregulated the matrix markers, SOX9 and aggrecan. However, this matrix response was not identified in dual-miRNA-bone marrow derived stem cells delivered to goat IVD organs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, these findings highlight the potential of nucleus pulposus cells as a regenerative cell source when combined with FLR-miRNA-149-5p mimic and 221-3p inhibitor for the treatment of LBP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI T2 Relaxation Time of the Intervertebral Disc: Repeatability, the Effect of Time of Day, and Unloaded Rest","authors":"Mackenzie N. Conner,&nbsp;Harrah R. Newman,&nbsp;John M. Peloquin,&nbsp;Edward J. Vresilovic,&nbsp;Dawn M. Elliott","doi":"10.1002/jsp2.70193","DOIUrl":"https://doi.org/10.1002/jsp2.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>T2 relaxation time is a widely used quantitative MRI measure of intervertebral disc degeneration, correlated with water and biochemical composition. T2 time is dependent on many factors, including scan parameters, signal decay model, and region(s) of interest, such that quantification of T2 time repeatability is necessary for interpreting T2 study outcomes. Further, the sensitivity of T2 time to factors such as time of day and unloaded rest has not been sufficiently quantified. The objective of this study was to evaluate repeatability, as well as time of day and unloaded rest effects on lumbar disc T2 relaxation time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young asymptomatic participants underwent MRI. Part 1 assessed intra-rater, inter-rater, and inter-scan Repeatability. Part 2 evaluated effects of Time of Day across four time points spanning 8 am to 5 pm, and 45 min unloaded Rest. T2 time was evaluated using a noise-corrected exponential decay model for a circular region of interest (ROI) in the nucleus pulposus (NP) and for 5 regions across a mid-sagittal line spanning the annulus fibrosus (AF), NP, and transition regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intra- and inter-rater repeatability was good-excellent (ICC = 0.76–0.99) across all regions. Inter-scan repeatability was good-excellent (ICC = 0.89–0.93) for the NP, while the AF had moderate-poor repeatability (ICC = 0.17–0.53). The minimal detectable change (MDC) for the NP ROI was 31 ms. Time of Day and Rest did not significantly affect NP T2 time. Across regions, all measured changes for Time of Day and Rest were less than corresponding MDCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>T2 time variability is primarily driven by acquisition factors, not rater subjectivity. Time of Day and Rest T2 time changes did not exceed within-subject variability (by MDC) and therefore are not critical considerations for some study designs. The reported MDCs provide practical thresholds for interpreting individual T2 time differences.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI T2 Relaxation Time of the Intervertebral Disc: Repeatability, the Effect of Time of Day, and Unloaded Rest","authors":"Mackenzie N. Conner,&nbsp;Harrah R. Newman,&nbsp;John M. Peloquin,&nbsp;Edward J. Vresilovic,&nbsp;Dawn M. Elliott","doi":"10.1002/jsp2.70193","DOIUrl":"https://doi.org/10.1002/jsp2.70193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>T2 relaxation time is a widely used quantitative MRI measure of intervertebral disc degeneration, correlated with water and biochemical composition. T2 time is dependent on many factors, including scan parameters, signal decay model, and region(s) of interest, such that quantification of T2 time repeatability is necessary for interpreting T2 study outcomes. Further, the sensitivity of T2 time to factors such as time of day and unloaded rest has not been sufficiently quantified. The objective of this study was to evaluate repeatability, as well as time of day and unloaded rest effects on lumbar disc T2 relaxation time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young asymptomatic participants underwent MRI. Part 1 assessed intra-rater, inter-rater, and inter-scan Repeatability. Part 2 evaluated effects of Time of Day across four time points spanning 8 am to 5 pm, and 45 min unloaded Rest. T2 time was evaluated using a noise-corrected exponential decay model for a circular region of interest (ROI) in the nucleus pulposus (NP) and for 5 regions across a mid-sagittal line spanning the annulus fibrosus (AF), NP, and transition regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intra- and inter-rater repeatability was good-excellent (ICC = 0.76–0.99) across all regions. Inter-scan repeatability was good-excellent (ICC = 0.89–0.93) for the NP, while the AF had moderate-poor repeatability (ICC = 0.17–0.53). The minimal detectable change (MDC) for the NP ROI was 31 ms. Time of Day and Rest did not significantly affect NP T2 time. Across regions, all measured changes for Time of Day and Rest were less than corresponding MDCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>T2 time variability is primarily driven by acquisition factors, not rater subjectivity. Time of Day and Rest T2 time changes did not exceed within-subject variability (by MDC) and therefore are not critical considerations for some study designs. The reported MDCs provide practical thresholds for interpreting individual T2 time differences.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Features of Discogenic Low Back Pain: A Narrative Review and Suggested Areas for Future Research and Clinical Practice","authors":"William Roger Peters,&nbsp;Ashish D. Diwan,&nbsp;Mario Giuseppe Zotti","doi":"10.1002/jsp2.70195","DOIUrl":"https://doi.org/10.1002/jsp2.70195","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain is a leading cause of global disability, with discogenic low back pain (DLBP), mechanically stimulated pain arising from the intervertebral disc, representing an important but often under-recognized subtype. DLBP arises from chronic structural and metabolic changes within the intervertebral disc, leading to inflammation, nerve ingrowth, and nociceptive sensitization. Diagnosis remains difficult due to overlapping symptoms, non-specific imaging, and the lack of a universally accepted reference standard. Accurate identification is critical for guiding effective management. This review aims to summarize and evaluate current and proposed diagnostic features of DLBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative literature review was conducted using PubMed, Scopus, and Web of Science, with supplementary hand searching and citation tracking. Studies evaluating clinical or investigative diagnostic features of DLBP were included, without restriction on study design. Studies involving neural compression, radiculopathy, or non-DLBP were excluded. Evidence was thematically synthesized, with preference given to higher-quality or larger studies where findings overlapped.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No clinical features have been consistently validated as predictive of DLBP. Flexion-based postures, movements, and prolonged sitting demonstrate modest diagnostic value, while traditional features such as axial loading or Valsalva maneuvers lack supporting evidence. Imaging findings, including Modic changes, high-intensity zones, and Pfirrmann grading, show limited specificity. Provocative discography is constrained by invasiveness, complications, and questionable reliability. Emerging metabolic imaging techniques demonstrate early potential as future reference standards. Evidence of clinical prediction models for DLBP remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DLBP diagnosis remains constrained by non-specific features and imperfect reference standards. Emerging metabolic imaging techniques warrant further validation, alongside development of robust diagnostic models to improve clinical decision making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal Implant–Associated Infection in Type 2 and Type 1 Diabetes: Phenotype-Specific Inflammatory Features and Therapeutic Response to Semaglutide","authors":"Thomas E. Olson,&nbsp;Trevor S. Lloyd,&nbsp;Christopher D. Hamad,&nbsp;Rene F. Chun,&nbsp;Joshua Wiener,&nbsp;Autreen Golzar,&nbsp;Joshua Mehany,&nbsp;Soroush Shahamatdar,&nbsp;Andrew Kittredge,&nbsp;Lauren Pearce,&nbsp;Kevin P. Francis,&nbsp;Farres Obeidin,&nbsp;Langston T. Holly,&nbsp;Michael R. Yeaman,&nbsp;John S. Adams,&nbsp;Nicholas M. Bernthal,&nbsp;William L. Sheppard","doi":"10.1002/jsp2.70196","DOIUrl":"https://doi.org/10.1002/jsp2.70196","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes mellitus (DM) is a major risk factor for postoperative infection and wound complications in spine surgery, yet distinctions between Type 2 (T2DM) and Type 1 (T1DM) pathophysiology are rarely addressed. This study compares infectious burden, wound healing, and immune response among a murine model of spinal implant-associated infection of T2DM, T1DM, and nondiabetic control mice before and after metabolic intervention with the GLP-1 receptor agonist (GLP-1RA), semaglutide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6J mice were rendered diabetic by streptozotocin induction (T1DM) or a high-fat, high-sucrose diet (T2DM). Spinal implants were placed and inoculated with bioluminescent <i>Staphylococcus aureus</i>. Infection progression was monitored longitudinally by in vivo bioluminescence imaging. Systemic inflammation was characterized through multiplex cytokine profiling, and paraspinal tissues were analyzed by histology and multiplex immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both diabetic models demonstrated greater infection burden, delayed wound healing, and distinct systemic inflammatory profiles compared with controls. T2DM was characterized by chronically elevated baseline inflammation and a blunted acute response to infection, whereas T1DM exhibited low baseline activity but exaggerated and dysregulated cytokine induction. Semaglutide attenuated infection severity, improved wound integrity, and partially normalized inflammatory patterns. Histology and immunofluorescence corroborated these findings, showing reduced immune cell infiltration and improved tissue organization in semaglutide-treated cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>T2DM and T1DM are associated with differing inflammatory and immune features in murine spinal implant–associated infection. Metabolic modulation with semaglutide restores immune balance, reduces infection severity, and promotes wound repair. These findings support exploration of GLP-1RA-based therapies to improve surgical outcomes in diabetic patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Features of Discogenic Low Back Pain: A Narrative Review and Suggested Areas for Future Research and Clinical Practice","authors":"William Roger Peters,&nbsp;Ashish D. Diwan,&nbsp;Mario Giuseppe Zotti","doi":"10.1002/jsp2.70195","DOIUrl":"https://doi.org/10.1002/jsp2.70195","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain is a leading cause of global disability, with discogenic low back pain (DLBP), mechanically stimulated pain arising from the intervertebral disc, representing an important but often under-recognized subtype. DLBP arises from chronic structural and metabolic changes within the intervertebral disc, leading to inflammation, nerve ingrowth, and nociceptive sensitization. Diagnosis remains difficult due to overlapping symptoms, non-specific imaging, and the lack of a universally accepted reference standard. Accurate identification is critical for guiding effective management. This review aims to summarize and evaluate current and proposed diagnostic features of DLBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A narrative literature review was conducted using PubMed, Scopus, and Web of Science, with supplementary hand searching and citation tracking. Studies evaluating clinical or investigative diagnostic features of DLBP were included, without restriction on study design. Studies involving neural compression, radiculopathy, or non-DLBP were excluded. Evidence was thematically synthesized, with preference given to higher-quality or larger studies where findings overlapped.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No clinical features have been consistently validated as predictive of DLBP. Flexion-based postures, movements, and prolonged sitting demonstrate modest diagnostic value, while traditional features such as axial loading or Valsalva maneuvers lack supporting evidence. Imaging findings, including Modic changes, high-intensity zones, and Pfirrmann grading, show limited specificity. Provocative discography is constrained by invasiveness, complications, and questionable reliability. Emerging metabolic imaging techniques demonstrate early potential as future reference standards. Evidence of clinical prediction models for DLBP remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DLBP diagnosis remains constrained by non-specific features and imperfect reference standards. Emerging metabolic imaging techniques warrant further validation, alongside development of robust diagnostic models to improve clinical decision making.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal Implant–Associated Infection in Type 2 and Type 1 Diabetes: Phenotype-Specific Inflammatory Features and Therapeutic Response to Semaglutide","authors":"Thomas E. Olson,&nbsp;Trevor S. Lloyd,&nbsp;Christopher D. Hamad,&nbsp;Rene F. Chun,&nbsp;Joshua Wiener,&nbsp;Autreen Golzar,&nbsp;Joshua Mehany,&nbsp;Soroush Shahamatdar,&nbsp;Andrew Kittredge,&nbsp;Lauren Pearce,&nbsp;Kevin P. Francis,&nbsp;Farres Obeidin,&nbsp;Langston T. Holly,&nbsp;Michael R. Yeaman,&nbsp;John S. Adams,&nbsp;Nicholas M. Bernthal,&nbsp;William L. Sheppard","doi":"10.1002/jsp2.70196","DOIUrl":"https://doi.org/10.1002/jsp2.70196","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes mellitus (DM) is a major risk factor for postoperative infection and wound complications in spine surgery, yet distinctions between Type 2 (T2DM) and Type 1 (T1DM) pathophysiology are rarely addressed. This study compares infectious burden, wound healing, and immune response among a murine model of spinal implant-associated infection of T2DM, T1DM, and nondiabetic control mice before and after metabolic intervention with the GLP-1 receptor agonist (GLP-1RA), semaglutide.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6J mice were rendered diabetic by streptozotocin induction (T1DM) or a high-fat, high-sucrose diet (T2DM). Spinal implants were placed and inoculated with bioluminescent <i>Staphylococcus aureus</i>. Infection progression was monitored longitudinally by in vivo bioluminescence imaging. Systemic inflammation was characterized through multiplex cytokine profiling, and paraspinal tissues were analyzed by histology and multiplex immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both diabetic models demonstrated greater infection burden, delayed wound healing, and distinct systemic inflammatory profiles compared with controls. T2DM was characterized by chronically elevated baseline inflammation and a blunted acute response to infection, whereas T1DM exhibited low baseline activity but exaggerated and dysregulated cytokine induction. Semaglutide attenuated infection severity, improved wound integrity, and partially normalized inflammatory patterns. Histology and immunofluorescence corroborated these findings, showing reduced immune cell infiltration and improved tissue organization in semaglutide-treated cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>T2DM and T1DM are associated with differing inflammatory and immune features in murine spinal implant–associated infection. Metabolic modulation with semaglutide restores immune balance, reduces infection severity, and promotes wound repair. These findings support exploration of GLP-1RA-based therapies to improve surgical outcomes in diabetic patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148110659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"9 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148079708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}