Bone最新文献

{"title":"Urinary phthalate metabolites associated with bone mineral density in adults: Data from the NHANES 2011–2018","authors":"Jian Yang ,&nbsp;Yanan Feng","doi":"10.1016/j.bone.2024.117287","DOIUrl":"10.1016/j.bone.2024.117287","url":null,"abstract":"<div><div>Phthalates (PAEs) are common environmental endocrine disruptors and environmental bone poisons that can reduce bone mineral density (BMD). The purpose of this study is to investigate whether the concentration of PAE metabolites in urine is related to BMD in many parts of adult bones. We examined a series of cross-sectional data of male (<em>n</em> = 1835) and female (<em>n</em> = 1756) participants aged 18 to 59 years old in the National Health and Nutrition Examination Survey from 2011 to 2018 and measured urine PAE metabolites and dual-energy X-ray absorption to determine BMD (total body, lumbar spine, and pelvis). We used linear regression to test the correlation between a single phthalate biomarker and BMD. After adjusting all confounding variables, MEHP was positively correlated with BMD of total body, lumbar spine and pelvis, and BMD levels of the total body, lumbar spine and pelvis decreased with the increase of MECPP concentration. We used the restricted cubic spline function to test the nonlinear correlation between PAE biomarkers and BMD. The results show that urinary PAE metabolites have a nonlinear relationship with total body BMD, lumbar spine BMD, and pelvic BMD. With the increase in the PAE concentration, the BMD level first increased and then decreased, showing an inverted U-shaped trend (<em>P</em> &lt; 0.05). Gender stratification also shows the same related trend. PAEs may be related to the BMD of adults. When the concentration of PAEs increases to a certain threshold, it will lead to a significant decrease in BMD.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117287"},"PeriodicalIF":3.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445529","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":"Is decreased psoas volume a risk factor for hip fracture? A comparative study of patients with and without hip fractures using the exact matching technique","authors":"Hee Chung Chung ,&nbsp;Woorim Choi ,&nbsp;Chul-Ho Kim ,&nbsp;Ji Wan Kim","doi":"10.1016/j.bone.2024.117278","DOIUrl":"10.1016/j.bone.2024.117278","url":null,"abstract":"<div><h3>Introduction</h3><div>Sarcopenia is linked to increased fall and hip fracture risk. However, studies often overlook comprehensively controlling for age, sex, bone mineral density (BMD), and body mass index (BMI). Our study aimed to determine if sarcopenia, determined by evaluating the psoas muscle volume, is an independent risk factor for hip fractures. We employed a methodological approach that includes the exact matching technique.</div></div><div><h3>Methods</h3><div>In this cross-sectional comparative study, we compared the data of patients who sustained hip fractures between 2015 and 2021 with those of a control group from a health screening center in a single center. The study included 545 patients with hip fractures and 1292 without fractures. We collected data on demographics, BMD determined using dual-energy X-ray absorptiometry, and abdominal and pelvic computed tomography (APCT) scans for psoas muscle volume analysis.</div></div><div><h3>Results</h3><div>The analysis after exact matching of 266 pairs revealed that psoas volume/height² was the most significant and dominant risk factor among the evaluated indices. Multivariate logistic regression analysis, adjusting for age, sex, BMI, and BMD, identified height or height²-adjusted psoas muscle volume as an independent risk factor for hip fractures (<em>p</em> = 0.042 and <em>p</em> = 0.002, respectively). Age, female sex, lower BMI, and lower BMD were associated with an increased risk of hip fractures.</div></div><div><h3>Conclusion</h3><div>Decreased psoas muscle volume adjusted for patient height independently predicts hip fracture risk. Psoas volume assessment via APCT is a practical tool for identifying at-risk individuals, emphasizing the necessity of including sarcopenia in hip fracture risk assessments.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117278"},"PeriodicalIF":3.5,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483031","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":"A novel genetic mouse model of osteoporosis with double heterozygosity of Irx3 and Irx5 characterizes sex-dependent phenotypes in bone homeostasis","authors":"Xinyu Chen ,&nbsp;Zhengchao Dou ,&nbsp;Joe Eun Son ,&nbsp;Meng Duan ,&nbsp;Fei Yang ,&nbsp;Shankuan Zhu ,&nbsp;Chi-Chung Hui","doi":"10.1016/j.bone.2024.117282","DOIUrl":"10.1016/j.bone.2024.117282","url":null,"abstract":"<div><div><em>Iroquois</em> homeobox gene 3 (<em>Irx3</em>) and <em>Irx5</em> encode transcription factors that play crucial roles in limb development and bone formation. Previous studies using knockout mice have revealed a role of <em>Irx3</em> and <em>Irx5</em> in osteogenesis in young adult mice. However, whether these genes are also essential for bone homeostasis in adulthood and contribute to bone diseases remain poorly understood. Osteoporosis is a disease characterized by lower bone mineral density and disrupted bone microarchitecture, typically occurs in postmenopausal women. Here, we demonstrate that <em>Irx3</em>/<em>5</em>^dHet mice with a half-reduction of <em>Irx3</em> and <em>Irx5</em> dosage serve as a novel model of osteoporosis. By micro-computed tomography, we found that <em>Irx3</em>/<em>5</em>^dHet mice exhibited sex-dependent bone loss patterns. While male <em>Irx3</em>/<em>5</em>^dHet mice progressively lost trabecular microstructures with aging, female mutants exhibited lower bone mineral density (BMD) and bone volume fraction (BV/TV) at early adulthood (9–15 weeks old) but without further loss later at 1 year of age. Bone marrow adipocytes are known to be elevated at the expenses of lower osteogenesis in osteoporotic bone marrow. Surprisingly, we found sex-dependent changes in adipogenesis at the age of skeletal maturity that bone marrow adipocytes were reduced in female <em>Irx3</em>/<em>5</em>^dHet mice along with deteriorated osteogenesis, while male mice exhibited elevated adipogenesis. In summary, we reported a novel genetic model for osteoporosis-like phenotypes, highlighting sex-dependent bone mineral density and bone marrow adipocyte characteristics.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117282"},"PeriodicalIF":3.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445528","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":"The role of AKR1B10 in osteogenic differentiation of mesenchymal stem cells and atrophic nonunion","authors":"Jie Wu ,&nbsp;Runze Li ,&nbsp;Chen Liu ,&nbsp;Weiming Li","doi":"10.1016/j.bone.2024.117284","DOIUrl":"10.1016/j.bone.2024.117284","url":null,"abstract":"<div><div>Atrophic nonunion is a chronic disease without effective medications. Here, high-throughput mRNA sequencing was used to explore the novel targets in atrophic nonunion. AKR1B10, a member of aldo-keto reductase family 1, is upregulated in atrophic nonunion tissues. There are currently no studies to reveal the role of AKR1B10 in atrophic nonunion. We used rat bone marrow-derived mesenchymal stem cells (BMSCs) to explore the effect of AKR1B10 on the osteogenic differentiation and autophagy. In vivo, we implanted collagen sponges loaded with LV-shAKR1B10-transduced BMSCs into rat fractured femurs to explore the role of AKR1B10 in fracture healing. The results showed that AKR1B10 reduced the activity of ALP, suppressed the expression of COL1A1, RUNX2 and OCN, and inhibited calcification deposition in osteogenically differentiated BMSCs. AKR1B10 reduced the expression of LC3II, decreased the number of autophagosomes, and promoted the expression of p62. In addition, the promoting effect of AKR1B10 knockdown on osteogenic differentiation of BMSCs was attenuated by 3-MA treatment. Implantation of collagen sponges found that knockdown of AKR1B10 promoted bone fracture healing. In conclusion, AKR1B10 inhibited the osteogenic differentiation and autophagy, and delayed the bone fracture healing. These results provide a new perspective on revealing the role of AKR1B10 in nonunion and may also provide a new therapeutic target for the treatment of nonunion.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117284"},"PeriodicalIF":3.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483033","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":"What personal factors are associated with osteoporosis, fragility fracture, and osteopenia? A population-level analysis using the United Kingdom Biobank","authors":"Elizabeth Duckworth ,&nbsp;Romil Shah ,&nbsp;Colin O'Neill ,&nbsp;Eeric Truumees ,&nbsp;Vagheesh Narasimhan ,&nbsp;Prakash Jayakumar","doi":"10.1016/j.bone.2024.117277","DOIUrl":"10.1016/j.bone.2024.117277","url":null,"abstract":"<div><h3>Purpose</h3><div>Osteopenia, osteoporosis, and fragility fractures pose a major public health concern. Population-level clinical and biopsychosocial data may uncover modifiable risk factors to target when developing whole person approaches to managing these conditions. The purpose of this study was to identify personal risk factors associated with osteoporosis, fragility fractures, and osteopenia from the United Kingdom Biobank (UKB) – a large population-level database.</div></div><div><h3>Methods</h3><div>We performed a cross-sectional study using the UKB to evaluate the association between 39 systematically selected explanatory variables with a diagnosis of osteopenia, osteoporosis, or fragility fracture. Bivariate analysis was performed followed by multivariable logistic regression adjusting for multicollinearity using covariance testing.</div></div><div><h3>Results</h3><div>Of 502,507 patients in the UKB, 40,657 had complete bone mineral density information from DEXA scans, and 32,193 had sustained a fragility fracture in the previous five years. In multivariable regression, increased time spent watching television (OR 1.15), living in an area with a high index of deprivation (OR 1.14), infrequent visits from friends and family (OR 1.09), experiencing symptoms of anxiety (OR 1.09), experiencing symptoms of depression (OR 1.08), and decreased exercise frequency (OR 1.03), were associated with increased risk of osteoporosis. Decreased exercise frequency (OR 1.27), increased BMI (OR 1.2), living in an area with a high index of deprivation (OR 1.11), and decreased salary (OR 1.10) were associated with increased risk of fragility fracture. Symptoms of anxiety (OR 1.15), living in an area with a high index of deprivation (OR 1.13), and increased time spent watching television (OR 1.11), living alone (OR 1.08), and symptoms of depression (OR 1.06), were associated with increased risk of osteopenia (<em>p</em> &lt; 0.05 for all variables).</div></div><div><h3>Conclusion</h3><div>Analysis of population-level datasets reveal a range of modifiable mental, social, and lifestyle/behavioral health factors that can inform multidisciplinary team-based care, including strategies that respond to psychosocial concerns and sustaining healthy lifestyles and behaviors in patients experiencing osteoporosis, fragility fracture, and osteopenia. Future work should assess the impact of integrated, whole person management programs for these conditions on longitudinal outcomes.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117277"},"PeriodicalIF":3.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483030","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":"Therapeutic effect of bloodletting on bone deterioration induced by hypobaric hypoxia in young rats","authors":"Doudou Hao ,&nbsp;Suyuan Wang ,&nbsp;Lin Feng ,&nbsp;Suying Zhu ,&nbsp;Yang Zhong ,&nbsp;Fengying Zhang ,&nbsp;Yanli Chen ,&nbsp;Yongxing Fu ,&nbsp;Zhiyou Shi ,&nbsp;Feng Tang ,&nbsp;Yunhong Wu","doi":"10.1016/j.bone.2024.117281","DOIUrl":"10.1016/j.bone.2024.117281","url":null,"abstract":"<div><h3>Objectives</h3><div>High-altitude regions, comprising hypoxic condition, are associated with different altitude-induced pathologies, including a reduction in bone density. Elucidating the mechanisms underlying bone degradation in such environments and developing targeted interventions and therapeutics is important. Bloodletting therapy has promising clinical applications, but its effects on the skeletal system and bone homeostasis are not well understood. The aim of this study was to investigate the effects of a hypobaric hypoxia environment on specific femoral morphological and structural properties, including the bone volume, cortical thickness, and trabecular microarchitecture, in juvenile Sprague–Dawley (SD) rats, and to explore the potential modulating effects of a bloodletting intervention on these parameters.</div></div><div><h3>Methods</h3><div>Male SD rats, 6 weeks of age, were subjected to a simulated hypobaric hypoxia environment, replicating a 5000-m altitude, for 12 weeks. For the bloodletting intervention group, rats were subjected to a weekly 500 μL tail vein blood withdrawal. Micro-CT technology, hematoxylin and eosin staining, and tartrate-resistant acid phosphatase staining were employed to comprehensively assess the femoral microstructure, tissue architecture, and cellular morphology. Additionally, immunofluorescence analysis was conducted to quantify the expression of key proteins, and transcriptome analysis was performed to identify differentially expressed genes.</div></div><div><h3>Results</h3><div>Exposing rats to hypobaric hypoxia led to a significant reduction in the bone mineral content, trabecular bone number, and cortical bone thickness, suggesting a deterioration of bone microstructure. Additionally, the hypoxic environment upregulated the expression of RANKL and HIF-1α, while downregulating RUNX2 expression. Notably, although bloodletting intervention did not significantly reverse these bone structural changes, transcriptome analysis revealed its regulatory influence on the expression of key genes, particularly <em>Mmp2</em>, <em>Fosl2</em>, and <em>URS0000B2A65A</em>, which are implicated in pathways governing the hypoxic response, osteoclast differentiation, and PI3K–Akt signaling.</div></div><div><h3>Conclusion</h3><div>This study highlights the detrimental effect of hypobaric hypoxia on the bone microstructure of juvenile rats and underscores the therapeutic potential of bloodletting to ameliorate this condition. Additionally, our study on the regulatory mechanisms mediating the effects of bloodletting on gene expression offers new perspectives on bone alterations. It suggests promising avenues for the development of novel preventative measures and targeted therapies to address the challenges posed by related bone disorders.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117281"},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483029","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":"Comparison of PET/CT versus CT only in the assessment of new heterotopic ossification bone lesions in patients with fibrodysplasia ossificans progressiva","authors":"Dinko González Trotter,&nbsp;Jennifer McGinniss,&nbsp;Kusha Mohammadi,&nbsp;Bret J. Musser,&nbsp;Gary A. Herman,&nbsp;Scott Mellis,&nbsp;Aris N. Economides","doi":"10.1016/j.bone.2024.117280","DOIUrl":"10.1016/j.bone.2024.117280","url":null,"abstract":"<div><div>Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder characterized by the deposition of bone in soft tissues, known as heterotopic ossification (HO). This post hoc analysis compared the performance of two imaging modalities for the detection and volumetric measurement of new HO lesions. LUMINA-1, a phase 2, randomized, double-blind study (NCT03188666), evaluated the safety and efficacy of garetosmab, an anti-activin A antibody, versus placebo in adult patients with FOP. From baseline through to week 28, ¹⁸F-labeled sodium fluoride positron emission tomography (PET)/X-ray computed tomography (CT) and CT-only scans prospectively acquired during the initial placebo-controlled period of the study were independently reviewed by two sets of fixed blinded readers plus an adjudicator for the presence and volume of new HO lesions. The number of patients with new lesions was 14/44 (31.8 %) and 12/44 (27.3 %) as detected by PET/CT and CT only, respectively. The aggregate number/volume of new lesions were very similar both for the placebo and the garetosmab group between PET/CT (27/245.0 cm³ and 3/21.3 cm³, respectively) and CT only (37/261.8 cm³ and 1/0.1 cm³, respectively). The mean (standard deviation) number of new lesions per patient by PET/CT through week 28 was 0.68 (1.57) versus 0.86 (1.95) as detected by CT only. Through week 28, the mean (standard deviation) volume of new lesions per patient detected by PET/CT was 6.05 (14.88) cm³ versus 5.94 (21.13) cm³ by CT only. Moderate agreement between PET/CT and CT-only detection was observed when identifying patients with new lesions, with a kappa coefficient of 0.46 (standard error, 0.146; 95 % confidence interval, 0.17–0.74). CT-only imaging showed similar performance to PET/CT in the detection and characterization of new HO lesions. CT-only imaging therefore is a viable option for the assessment of therapies on new HO in patients with FOP.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117280"},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483017","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":"Stress fracture of bone under physiological multiaxial cyclic loading: Activity-based predictive models","authors":"Winson T. George ,&nbsp;Shayom Debopadhaya ,&nbsp;Samuel J. Stephen ,&nbsp;Bryan A. Botti ,&nbsp;David B. Burr ,&nbsp;Deepak Vashishth","doi":"10.1016/j.bone.2024.117279","DOIUrl":"10.1016/j.bone.2024.117279","url":null,"abstract":"<div><div>While it is known that excessive accumulation of fatigue damage from daily activities contributes to fracture, a model of bone failure under physiologically relevant multiaxial cyclic loading needs to be developed in order to develop effective management strategies for stress or fatigue fractures. The role of strain-induced damage from repetitive loading is a strong candidate for such a model, as cycles of mechanical loading leading to failure can be measured directly. However, this approach has been limited by the restrictions of uniaxial loading models, which often overestimates the fatigue life of bone and suggests that bone will only break well beyond the realistic limits of exercise. To address this gap and develop a physiologically relevant model, our study leverages the power of four commonly used engineering failure criteria as a model for multiaxial loading using a cohort of human tibiae from cadaveric donors (age range 21–85 years old). Four failure criteria (Von Mises, Tsai-Wu, Findley critical plane, and maximum shear strain) were found to be effective <em>in vitro</em> models of tibial fracture when age groups of donors were combined (r² &gt; 0.84) and stratified (younger: 21–52-years-old <em>versus</em> older: 57–85-years-old) (r² &gt; 0.83) (<em>p</em> &lt; 0.001). Each failure criterion displayed distinctly lower fatigue curves for the older age group. The maximum shear strain model was used to determine the efficacy of this approach to predict fatigue fractures in humans using published <em>in vivo</em> data from human volunteers. Consistent with <em>in vivo</em> observations in general population, the model demonstrated failure at 5000 to 200,000 loading cycles depending on activities such as jumping, sprinting, and walking, with a 3-fold reduction of fatigue life in older donors. These findings dramatically improve estimates of fatigue life under repetitive loading and demonstrate how age-related changes in bone significantly increase its propensity for fatigue-induced fractures.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117279"},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407364","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":"Piezo1 expression in mature osteocytes is dispensable for the skeletal response to mechanical loading","authors":"Xuehua Li ,&nbsp;Connie Zhang ,&nbsp;Cameron E. Vail ,&nbsp;John T. Sherrill ,&nbsp;Jinhu Xiong","doi":"10.1016/j.bone.2024.117276","DOIUrl":"10.1016/j.bone.2024.117276","url":null,"abstract":"<div><div>Mechanical loading is essential for bone growth and homeostasis, with osteocytes considered the primary mechanosensors. Deleting the mechanosensitive ion channel Piezo1 from Dmp1-Cre-targeted cells, which include both osteoblasts and osteocytes, resulted in reduced bone mass and impaired skeletal responses to mechanical stimuli. To specifically isolate Piezo1's role in osteocytes, we used Sost-Cre mice to generate mice with Piezo1 deletion exclusively in mature osteocytes. These mice exhibited lower bone mineral density, decreased cancellous bone mass, and reduced cortical thickness with decrease periosteal expansion. However, unlike mice lacking Piezo1 in both osteoblasts and osteocytes, those with Piezo1 deletion in mature osteocytes responded normally to mechanical loading. These findings suggest that Piezo1 expression in mature osteocytes contributes to bone maintenance under normal physiological condition, but is dispensable for the skeletal response to mechanical loading.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117276"},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402328","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":"Macrophage-derived amphiregulin promoted the osteogenic differentiation of chondrocytes through EGFR/Yap axis and TGF-β activation","authors":"Xinyi Wang,&nbsp;Shuo Wang,&nbsp;Hailin Mu,&nbsp;Chang Yang,&nbsp;Wei Dong,&nbsp;Xinru Wang,&nbsp;Jiawei Wang","doi":"10.1016/j.bone.2024.117275","DOIUrl":"10.1016/j.bone.2024.117275","url":null,"abstract":"<div><div>Endochondral ossification represents a crucial biological process in skeletal development and bone defect repair. Macrophages, recognized as key players in the immune system, are now acknowledged for their substantial role in promoting endochondral ossification within cartilage. Concurrently, the epidermal growth factor receptor (EGFR) ligand amphiregulin (Areg) has been documented for its contributory role in restoring bone tissue homeostasis post-injury. However, the mechanism by which macrophage-secreted Areg facilitates bone repair remains elusive. In this study, the induction of macrophage depletion through in vivo administration of clodronate liposomes was employed in a standard open tibial fracture mouse model to assess bone healing using micro-computed tomography (micro-CT) analysis, histomorphology, and ELISA serum evaluations. The investigation revealed sustained expression of Areg during the fracture healing period in wild-type mice. Macrophage depletion significantly reduced the number of macrophages on the local bone surface and vital organs. This reduction led to diminished Areg secretion, decreased collagen production, and delayed fracture healing. However, histological and micro-CT assessments at 7 and 21 days post-local Areg treatment exhibited a marked improvement of bone healing compared to the vehicle control. In vitro studies demonstrated an increase of Areg secretion by the Raw264.7 cells upon ATP stimulation. Indirect co-culture of Raw264.7 and ATDC5 cells indicated that Areg overexpression enhanced the osteogenic potential of chondrocytes, and vice versa. This osteogenic promotion was attributed to Areg's activation of the membrane receptor EGFR in the ATDC5 cell line, the enhanced phosphorylation of transcription factor Yap, and the facilitation of the expression of bioactive TGF-β by chondrocytes. Collectively, this research elucidates the direct mechanistic effects of macrophage-secreted Areg in promoting bone homeostasis following bone injury.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117275"},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395935","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}