Journal of Bone Oncology最新文献

{"title":"Osteofibrous dysplasia, osteofibrous Dysplasia-Like adamantinoma, and adamantinoma: A Single-center retrospective analysis","authors":"Wei Chen ,&nbsp;Qinglin Jin ,&nbsp;Shaohua Du ,&nbsp;Shuangwu Dai ,&nbsp;Changhe Hou ,&nbsp;Zixiong Lei ,&nbsp;Lin Zhong ,&nbsp;Qingzhu Wei ,&nbsp;Haomiao Li","doi":"10.1016/j.jbo.2025.100700","DOIUrl":"10.1016/j.jbo.2025.100700","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to comprehensively investigate and contrast the imaging manifestations, pathological features, surgical interventions, and prognostic outcomes of <strong>Osteofibrous Dysplasia(OFD)</strong>, <strong>Osteofibrous Dysplasia-Like Adamantinoma(OFD-AD)</strong>, and <strong>Adamantinoma(AD)</strong>. By synthesizing disease profiles and exploring their evolutionary relationships, we sought to identify more effective diagnostic and therapeutic strategies for these conditions.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on patients diagnosed with OFD, OFD-AD, or AD at our institution between 2015 and 2022. The analysis included a detailed comparison of clinical presentations, imaging findings, and pathological characteristics. We also evaluated the impact of different diagnostic and treatment modalities on patient prognosis and explored potential disease evolution and transformation patterns.</div></div><div><h3>Results</h3><div>Fifty patients were included in this study: 16 with OFD, 27 with OFD-AD, and 7 with AD. The median age of onset was 14 years for OFD, 6 years for OFD-AD, and 33 years for AD. All diagnoses were confirmed through a combination of clinical evaluation, imaging (X-rays and MRI), and pathological examination. Among the patients, 2 (both with OFD-AD) were managed with observation only. Thirty-seven patients underwent intralesional resection (16 OFD, 20 OFD-AD, and 1 AD), and 11 patients had complete resection (5 OFD-AD and 6 AD). After a minimum follow-up of 24 months (range: 24–––90 months, median: 56 months), 12 patients experienced tumor recurrence (OFD: 2/16, 12.5 %; OFD-AD: 9/25, 36 %; AD: 1/6, 17 %). One patient had concurrent OFD-AD in the fibula and AD in the tibia. In another case, an OFD-AD recurrence 4 years after surgery was later diagnosed as OFD, and an OFD recurrence 2 years after surgery was reclassified as OFD-AD. No distant metastases were observed in any patient.</div></div><div><h3>Conclusion</h3><div>OFD, OFD-AD, and AD exhibit similarities in clinical and imaging presentations, and their pathological features may represent different stages of a common lesion’s evolution. These diseases have distinct age − related onset patterns and variable recurrence risks. Thus, accurate diagnosis and personalized treatment strategies based on patient characteristics are crucial for effective disease management.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100700"},"PeriodicalIF":3.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519166","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":"Demethylzeylasteral inhibits proliferation and metastasis of osteosarcoma cells by modulating the PI3K/AKT/Autophagy pathways","authors":"Xuhui Yuan ,&nbsp;Jiayu Li ,&nbsp;Bo Yu ,&nbsp;Feng Cai ,&nbsp;Binqi Chen ,&nbsp;Jun Liu ,&nbsp;Yuanxiang Peng ,&nbsp;Duo Zeng ,&nbsp;Qi Liao ,&nbsp;Lang Liu","doi":"10.1016/j.jbo.2025.100699","DOIUrl":"10.1016/j.jbo.2025.100699","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) remains a highly aggressive malignancy with limited treatment options, necessitating the discovery of novel therapeutic agents. Demethylzeylasteral (DEM), a compound previously shown to exert anti-tumor properties in several malignancies, has not been sufficiently explored for its potential in OS treatment.</div></div><div><h3>Purpose</h3><div>This study focused on the anti-tumor properties of DEM on OS cells as well as the potential mechanisms.</div></div><div><h3>Methods</h3><div>OS cell lines (MG63 and 143B) were exposed to varying concentrations of DEM, followed by assessment of diverse cell functions. RNA sequencing was implemented to identify the molecular pathways affected by DEM exposure. The mechanistic underpinnings of DEM’s action were also studied via a series of assays. Additionally, the therapeutic potential was validated utilizing xenograft models.</div></div><div><h3>Results</h3><div>DEM evidently repressed OS cell proliferation in a dose- and time-dependent fashion, arrested cells in G2/M phase, and facilitated apoptosis through the modulation of the BCL2/BAX ratio. Furthermore, DEM suppressed cell migration and invasion by reversing EMT-related protein expression. RNA sequencing revealed that DEM primarily affected autophagy-related pathways, particularly through the PI3K/AKT signaling. DEM treatment led to an elevation in ROS generation and enhanced autophagic activity, as demonstrated by elevated LC3B puncta formation and autophagy-related protein expression. <em>In vivo</em>, DEM effectively suppressed tumor growth while showing a favorable safety profile.</div></div><div><h3>Conclusion</h3><div>This study provides comprehensive evidence that DEM exerts potent anti-tumor properties in OS via the PI3K/AKT pathway, highlighting the significance of DEM as a therapeutic candidate for OS.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100699"},"PeriodicalIF":3.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480640","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":"Exploring bone-tumor interactions through 3D in vitro models: Implications for primary and metastatic cancers","authors":"Nicolas Cristini ,&nbsp;Mohamadreza Tavakoli ,&nbsp;Mehdi Sanati ,&nbsp;Saber Amin Yavari","doi":"10.1016/j.jbo.2025.100698","DOIUrl":"10.1016/j.jbo.2025.100698","url":null,"abstract":"<div><div>Bone tissue serves as a perfect hosting site where metastatic cancer cells of the most prevalent cancer types, such as prostate and breast cancers, as well as the native bone sarcomas, can further proliferate, advancing the disease stage with the consequential decline of the patient’s prognosis. Understanding how the bone niche interacts with tumor cells and the mechanisms leading to drug resistance is a crucial step for enabling the identification of effective cancer therapies. Nevertheless, bone tumor research and the development of new effective anticancer drugs have been hampered for a long time due to the limitations of preclinical models. Traditional 2D cultures and animal models have failed to accurately replicate the human bone cancer microenvironment, driving researchers to develop 3D <em>in vitro</em> bone models using tissue-engineered bone constructs and advanced technologies like microfluidics and additive manufacturing. While a complete reproduction of the bone tumor microenvironment (TME), including all relevant cell types, stromal elements, and biophysical cues, remains elusive, targeted inclusion of key components has advanced the physiological relevance of these models. The following review evaluates the biomimetic approaches that have been used to recapitulate the bone TME through 3D <em>in vitro</em> models, with particular attention to recent studies aimed at more accurately mimicking the complexity of bone TME, highlighting future directions and the advancements required to overcome present limitations.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100698"},"PeriodicalIF":3.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314338","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":"Chondroblastoma of the femoral head:current and future therapeutic options","authors":"Jun Teng ,&nbsp;Yitong Ding ,&nbsp;Can Liu ,&nbsp;Yangfei Yi ,&nbsp;Jie Wen ,&nbsp;Sheng Xiao ,&nbsp;Xiaohong Jian ,&nbsp;Yufei Li","doi":"10.1016/j.jbo.2025.100697","DOIUrl":"10.1016/j.jbo.2025.100697","url":null,"abstract":"<div><div>Chondroblastoma of the femoral head is a benign tumor originating from immature chondrocytes (chondroblasts), also known as Codman’s tumor. This tumor is mainly located in the epiphysis of the end of long bones, especially in the region of the femoral head. It is more common in children and adolescents. Its etiology is derived from embryonic cartilage, or mutations in chondroblasts. The diagnosis mainly depends on imaging examination and histopathological examination. Surgical resection is the main treatment method, and there are also many new methods such as gene therapy and immunotherapy. This article reviews the etiology, diagnosis and treatment of chondroblastoma of the femoral head, so as to provide ideas and basis for further clinical research on adolescent chondroblastoma of the femoral head.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100697"},"PeriodicalIF":3.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144290499","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":"Long-term oncological and functional outcomes in patients with bone sarcomas in the proximal femur undergoing unplanned surgery: A single-center retrospective cohort study","authors":"Guodong Zhong ,&nbsp;Tiao Lin ,&nbsp;Yongqian Wang,&nbsp;Hao Yao,&nbsp;Aierxiding Aimaiti,&nbsp;Xianbiao Xie,&nbsp;Changye Zou,&nbsp;Junqiang Yin,&nbsp;Jingnan Shen,&nbsp;Gang Huang,&nbsp;Zhiqiang Zhao","doi":"10.1016/j.jbo.2025.100696","DOIUrl":"10.1016/j.jbo.2025.100696","url":null,"abstract":"<div><h3>Background</h3><div>The clinical and radiological presentation of bone sarcomas in the proximal femur is often atypical, frequently leading to diagnostic errors or inappropriate treatments. To our knowledge, no previous studies have analyzed reasons for or compared outcomes among patients with proximal femoral bone sarcomas undergoing unplanned surgery.</div></div><div><h3>Methods</h3><div>Patients with proximal femoral bone sarcomas treated at our institution between January 2013 and January 2023 were retrospectively reviewed, including those initially misdiagnosed or mismanaged. Overall survival (OS) and event-free survival (EFS) rates were analyzed using Kaplan-Meier curves and log-rank tests. Independent-samples and paired t-tests were used to compare Musculoskeletal Tumor Society (MSTS) scores, while chi-square tests were used to assess local recurrence rates (LRR).</div></div><div><h3>Results</h3><div>Of the 85 patients included, 27 cases underwent unplanned surgery at external hospitals, including 16 males and 11 females, with a median age of 44 years (range: 11–81 years). Initial preoperative radiologic findings in these patients undergoing unplanned surgery showed no periosteal reaction or soft tissue mass. No significant differences in OS, EFS, or LRR were observed between the unplanned and planned surgery groups (p &gt; 0.05). However, MSTS scores were significantly lower in the unplanned surgery group (p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Unplanned surgery correlates with poorer functional outcomes. Reducing its incidence requires not only improved diagnostic imaging but also increased clinical suspicion, adherence to standardized diagnostic protocols, and early referral to specialized sarcoma centers. A multidisciplinary approach by experienced teams may enhance diagnostic accuracy and surgical planning, thereby minimizing unplanned interventions.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100696"},"PeriodicalIF":3.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321874","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":"Regulatory role of the METTL3/MALAT1 axis in multiple myeloma progression","authors":"Xiaohong Lu,&nbsp;Yafei Li,&nbsp;Ruie Li,&nbsp;Jingheng Zhang,&nbsp;Jiayu Peng,&nbsp;Yan Zhang","doi":"10.1016/j.jbo.2025.100695","DOIUrl":"10.1016/j.jbo.2025.100695","url":null,"abstract":"<div><h3>Objective</h3><div>Methyltransferase-like 3 (METTL3) plays a crucial role in cancer progression, both in m6A modification-dependent and −independent pathways. We aimed to elucidate the mechanism by which METTL3 and the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contribute to the pathogenesis of multiple myeloma (MM).</div></div><div><h3>Methods</h3><div>Bone marrow samples were collected from 56 patients with MM and 42 healthy donors, followed by assessment of METTL3 and MALAT1 levels. An interaction between METTL3 and MALAT1 was also identified. METTL3- and MALAT1-related oligonucleotides were transfected into RPMI8226 and U266 cells to explore their role in cell growth. Apoptosis, migration, proliferation, and invasion of RPMI8226 and U266 cells were assayed.</div></div><div><h3>Results</h3><div>Elevated METTL3 and MALAT1 levels were observed in patients with MM. Interference with METTL3 or MALAT1 inhibited the malignant behavior of RPMI8226 and U266 cells. There was an interaction between METTL3 and MALAT1. Overexpression of MALAT1 reversed the inhibitory effects of METTL3 interference on tumor cell malignancy.</div></div><div><h3>Conclusion</h3><div>METTL3 augments MM development by enhancing MALAT1 expression.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100695"},"PeriodicalIF":3.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471504","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":"Impact of treatment delay of multiple myeloma bone disease on later myeloma-related skeletal events and outcome","authors":"Eskelinen Veera ,&nbsp;Niemi Pauli ,&nbsp;Partanen Anu ,&nbsp;Kangas Jaakko ,&nbsp;E.L.Kuusisto Milla","doi":"10.1016/j.jbo.2025.100693","DOIUrl":"10.1016/j.jbo.2025.100693","url":null,"abstract":"<div><div>Limited data exists on the effect of treatment delay of multiple myeloma (MM) bone disease on the disease course. In this real-world analysis of 625 patients with newly diagnosed MM (NDMM) we aimed to investigate the impact of delay in starting bone disease treatment on later skeletal events and outcome.</div><div>Altogether 480 (76.8 %) patients had bone disease at the diagnosis, 282 (45.1 %) patients had a fracture at diagnosis, and 181 (29.1 %) patients had a later fracture during the follow-up. A delay in the initiation of treatment of bone disease was experienced by 221 (35.4 %) patients and tooth extraction was a main reason for the delay. Patients with a delay seemed to experience earlier and more frequent later fractures. Also, a fracture (p = 0.003) or bone disease (p &lt; 0.001) at diagnosis predicted earlier incidence of later fractures. As a bone targeted treatment, altogether 363 (58.1 %) patients received zoledronic acid, 81 (13.0 %) denosumab and 134 (21.4 %) other bone-targeted treatment. Patients treated with denosumab had poorer overall survival (OS) (p &lt; 0.001) and experienced earlier later fractures (p = 0.003). Multivariate analysis showed that bone disease at diagnosis (p = 0.043) and given bone disease treatment (p = 0.023) significantly impacted on the time to next fracture. Regarding OS, delay in osteoprotective treatment (p = 0.004) and time of the diagnosis (p &lt; 0.001) were significant factors in multivariate analysis.</div><div>To conclude, this study suggests that early initiation of bone disease treatment seemed to prevent later fractures. These findings highlight the importance of patients’ rapid access to a dentist and the start of bone targeted treatment without delay after a myeloma diagnosis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100693"},"PeriodicalIF":3.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241901","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":"Glutathione peroxidase 7 knockdown inhibits growth, invasion, and migration while enhancing oxidative stress and ferroptosis in osteosarcoma cells","authors":"Runze He ,&nbsp;Xiao Xiao ,&nbsp;Xinwen Tang ,&nbsp;Chen Lv","doi":"10.1016/j.jbo.2025.100692","DOIUrl":"10.1016/j.jbo.2025.100692","url":null,"abstract":"<div><h3>Background</h3><div>Glutathione peroxidase 7 (GPX7) possesses antioxidant functions and plays a crucial role in regulating cancer progression. However, relevant evidence in osteosarcoma is scarce. The current study aimed to explore the effect of GPX7 on osteosarcoma progression, oxidative stress, and ferroptosis.</div></div><div><h3>Methods</h3><div>Human osteosarcoma cells (U2OS, MG-63, and SaOS-2) were transfected with GPX7 small interfering RNA (siGPX7). Proliferation, apoptosis, invasion, migration, oxidative stress markers, Fe²⁺ levels, and ferroptosis markers were detected in human osteosarcoma cells.</div></div><div><h3>Results</h3><div>GPX7 knockdown inhibited human osteosarcoma cell proliferation, as evidenced by reduced relative cell viability and 5-Ethynyl-2′-deoxyuridine positive cells. GPX7 knockdown also showed a certain ability to promote human osteosarcoma cell apoptosis, as evidenced by increased terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) positive rate and cleaved-caspase3. GPX7 knockdown decreased invasive and migration rates of human osteosarcoma cells. GPX7 knockdown increased reactive oxygen species and malondialdehyde but decreased mitochondrial membrane potential, suggesting that GPX7 knockdown enhanced oxidative stress in human osteosarcoma cells. Regarding ferroptosis markers, GPX7 knockdown increased acyl-CoA synthetase long-chain family member 4 and reduced solute carrier family 7 member 11; moreover, GPX7 knockdown increased Fe²⁺ levels; the above findings indicated that GPX7 knockdown promoted ferroptosis in human osteosarcoma cells.</div></div><div><h3>Conclusion</h3><div>GPX7 knockdown inhibits osteosarcoma cell growth, invasion, and migration while facilitating oxidative stress and ferroptosis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100692"},"PeriodicalIF":3.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480639","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":"Comparative analysis of X-ray, CT, and MRI images in patients with chondroblastoma in tubular and non-tubular bones","authors":"Xiang Feng ,&nbsp;Yuxiang Fang ,&nbsp;Hanhua Yu ,&nbsp;Zhanqiang Song ,&nbsp;Xiangrong Guo ,&nbsp;Man Yang","doi":"10.1016/j.jbo.2025.100691","DOIUrl":"10.1016/j.jbo.2025.100691","url":null,"abstract":"<div><h3>Objective</h3><div>To compare and analyze the image features of X-ray, computerized tomography (CT), and magnetic resonance imaging (MRI) in patients with chondroblastoma (CB) in tubular and non-tubular bones, to improve the preoperative diagnostic accuracy and follow-up the postoperative recurrence rate.</div></div><div><h3>Methods</h3><div>Sixty-one CB patients confirmed by surgical pathology in our hospital and Huazhong University of Science and Technology Tongji Medical College Affiliated Union Hospital from August 2013 to March 2024 were included in this study. Their clinical, image, and pathological data were retrospectively collected and analyzed. Clinical data included age and gender. Image data included lesion size, lobulation, distensibility, bone crest, calcification, sclerotic margin, periosteal reaction, soft tissue swelling, fluid level, and aneurysmal bone cyst (ABC). Pathologic data included pathological findings and immunohistochemistry (IHC).</div><div>Results</div><div>The average onset age in tubular bone and non-tubular bone groups was 17.3 ± 5.5 and 25.6 ± 5.7 respectively (<em>p</em> = 0.00). The percentage of distensibility with or without was 37 %, 63 %, 69 % and 31 % (<em>p</em> = 0.01), the percentage of bone crest with or without was 46 %, 54 %, 77 % and 20 % (<em>p</em> = 0.01), and the percentage of fluid level with or without was 17 %, 83 %, 62 % and 38 % in tubular bone and non-tubular bone groups, respectively (<em>p</em> = 0.00). CB was predominantly non-calcified or mottled calcification in patients with lesions less than 12 months and patchy or cloudy calcification in patients with lesions more than 12 months. CB of the calcaneus and talus accounted for 54 % of the CB of the non-tubular bones. There was one case of preoperative malignant lesion and one case of postoperative recurrence.</div></div><div><h3>Conclusion</h3><div>Lesions in CB patients in non-tubular bone are swollen and are prone to form a coarse bone creast and fluid level, and the bone swells even more obviously when CB is combined with ABC. There is a low possibility of malignant transformation and postoperative recurrence in CB patients.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100691"},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168091","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 metastatic role of the CXCL10-CXCR3 axis and its therapeutic potential in osteosarcoma","authors":"Benjamin B. Gyau ,&nbsp;Junyan Wang ,&nbsp;Xiang Chen ,&nbsp;Margaret A. Clement ,&nbsp;Zoe D. Man ,&nbsp;Angela M. Major ,&nbsp;Mathew C. Weiser ,&nbsp;Jun Xu ,&nbsp;John Hicks ,&nbsp;Tsz-Kwong Man","doi":"10.1016/j.jbo.2025.100690","DOIUrl":"10.1016/j.jbo.2025.100690","url":null,"abstract":"<div><div>The CXCL10-CXCR3 axis regulates immunity, tumorigenesis, and metastasis in multiple cancers. Yet, its roles in osteosarcoma (OS), the predominant pediatric malignant bone tumor, are not fully defined. Our prior work has shown that elevated serum CXCL10 levels correlate with poor OS prognosis. The current study delves deeper by investigating how CXCL10-mediated CXCR3 signaling influences OS growth and metastatic spread. <em>In vitro</em>, CXCL10 and related CXCR3 ligands (CXCL4, CXCL9, and CXCL11) enhanced OS tumor cell migration. In an orthotopic xenograft mouse model with a newly created CXCR3 knockout (KO) mutant, tumor growth and lung metastasis decreased significantly when compared with the parental cell line. Transfecting the transcript isoform CXCR3A, but not CXCR3B, into KO cells restored metastatic phenotypes in mice, highlighting isoform specificity. Pharmacological CXCR3 inhibition reduced OS cell migration <em>in vitro</em> and metastasis <em>in vivo</em>. Mechanistically, CXCL10 triggered AKT (S473) and PAK1 (S144) phosphorylation in OS cell lines, but not in the KO mutant, implicating the role of these kinases in CXCL10-mediated metastasis. Collectively, our data indicate the CXCL10-CXCR3 axis as a key metastatic driver in OS, suggesting CXCR3 as a viable therapeutic target for treating OS metastasis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"52 ","pages":"Article 100690"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147944","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}