Bone Research最新文献

KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-02 DOI: 10.1038/s41413-025-00415-2

Li Chen, Kaikai Shi, Nicholas Ditzel, Weimin Qiu, Michaela Tencerova, Louise Himmelstrup Dreyer Nielsen, Florence Figeac, Alexander Rauch, Yuhang Liu, Jiuyuan Tao, Veronika Sramkova, Lenka Rossmeislova, Greet Kerckhofs, Tatjana N. Parac-Vogt, Sébastien de Bournonville, Thomas Levin Andersen, Mikael Rydén, Moustapha Kassem

{"title":"KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism","authors":"Li Chen, Kaikai Shi, Nicholas Ditzel, Weimin Qiu, Michaela Tencerova, Louise Himmelstrup Dreyer Nielsen, Florence Figeac, Alexander Rauch, Yuhang Liu, Jiuyuan Tao, Veronika Sramkova, Lenka Rossmeislova, Greet Kerckhofs, Tatjana N. Parac-Vogt, Sébastien de Bournonville, Thomas Levin Andersen, Mikael Rydén, Moustapha Kassem","doi":"10.1038/s41413-025-00415-2","DOIUrl":"https://doi.org/10.1038/s41413-025-00415-2","url":null,"abstract":"An increasing number of studies have characterized the bone as an endocrine organ, and that bone secreted factors may not only regulate local bone remodeling, but also other tissues and whole-body metabolic functions. The precise nature of these regulatory factors and their roles at bridging the bone, bone marrow adipose tissue, extramedullary body fat and whole-body energy homeostasis are being explored. In this study, we report that KIAA1199, a secreted factor produced from bone and bone marrow, previously described as an inhibitor of bone formation, also plays a role at promoting adipogenesis. KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue, subcutaneous and visceral fat tissue mass, blood cholesterol, triglycerides, free fatty acids and glycerol, as well as improved insulin sensitivity in skeletal muscle, liver and fat. Moreover, these mice are protected from the detrimental effects of high-fat diet feeding, with decreased obesity, lower blood glucose and glucose tolerance, as well as decreased adipose tissue inflammation, insulin resistance and hepatic steatosis. In human studies, plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol, triglycerides, free fatty acids, glycerol, fasting glucose and HOMA-IR. Mechanistically, KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT / ERK signaling. These findings provide evidence for the role of bone secreted factors on coupling bone, fat and whole-body energy homeostasis.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"104 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-01 DOI: 10.1038/s41413-025-00412-5

Guanzhi Liu, Ruomu Cao, Qimeng Liu, Heng Li, Peng Yan, Kunzheng Wang, Run Tian, Pei Yang

{"title":"M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition","authors":"Guanzhi Liu, Ruomu Cao, Qimeng Liu, Heng Li, Peng Yan, Kunzheng Wang, Run Tian, Pei Yang","doi":"10.1038/s41413-025-00412-5","DOIUrl":"https://doi.org/10.1038/s41413-025-00412-5","url":null,"abstract":"Exosomes have shown good potential in ischemic injury disease treatments. However, evidence about their effect and molecular mechanisms in osteonecrosis of femoral head (ONFH) treatment is still limited. Here, we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes (M2-Exos). We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition. Additionally, we identified that M2-Exos’ therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adeno-associated virus respectively. Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells. These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"33 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Callus organoids reveal distinct cartilage to bone transition mechanisms across donors and a role for biological sex

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-26 DOI: 10.1038/s41413-025-00418-z

Isaak Decoene, Hanna Svitina, Mohamed Belal Hamed, Anastassios Economou, Steve Stegen, Frank P. Luyten, Ioannis Papantoniou

{"title":"Callus organoids reveal distinct cartilage to bone transition mechanisms across donors and a role for biological sex","authors":"Isaak Decoene, Hanna Svitina, Mohamed Belal Hamed, Anastassios Economou, Steve Stegen, Frank P. Luyten, Ioannis Papantoniou","doi":"10.1038/s41413-025-00418-z","DOIUrl":"https://doi.org/10.1038/s41413-025-00418-z","url":null,"abstract":"Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcomes. Recent insights into the mechanism of native bone repair highlight a robust path dependence. Organoid-based bottom-up developmental engineering mimics this path-dependence to design personalized living implants scaffold-free, with in-build outcome predictability. Yet, adequate (noninvasive) quality metrics of engineered tissues are lacking. Moreover, insufficient insight into the role of donor variability and biological sex as influencing factors for the mechanism toward bone repair hinders the implementation of such protocols for personalized bone implants. Here, male and female bone-forming organoids were compared to non-bone-forming organoids regarding their extracellular matrix composition, transcriptome, and secreted proteome signatures to directly link in vivo outcomes to quality metrics. As a result, donor variability in bone-forming callus organoids pointed towards two distinct pathways to bone, through either a hypertrophic cartilage or a fibrocartilaginous template. The followed pathway was determined early, as a biological sex-dependent activation of distinct progenitor populations. Independent of donor or biological sex, a cartilage-to-bone transition was driven by a common panel of secreted factors that played a role in extracellular matrix remodeling, mineralization, and attraction of vasculature. Hence, the secreted proteome is a source of noninvasive biomarkers that report on biological potency and could be the missing link toward data-driven decision-making in organoid-based bone tissue engineering.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"57 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tm4sf19 inhibition ameliorates inflammation and bone destruction in collagen-induced arthritis by suppressing TLR4-mediated inflammatory signaling and abnormal osteoclast activation

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-24 DOI: 10.1038/s41413-025-00419-y

Sujin Park, Kwiyeom Yoon, Eunji Hong, Min Woo Kim, Min Gi Kang, Seiya Mizuno, Hye Jin Kim, Min-Jung Lee, Hee Jae Choi, Jin Sun Heo, Jin Beom Bae, Haein An, Naim Park, Hyeyeon Park, Pyunggang Kim, Minjung Son, Kyoungwha Pang, Je Yeun Park, Satoru Takahashi, Yong Jung Kwon, Dong-Woo Kang, Seong-Jin Kim

{"title":"Tm4sf19 inhibition ameliorates inflammation and bone destruction in collagen-induced arthritis by suppressing TLR4-mediated inflammatory signaling and abnormal osteoclast activation","authors":"Sujin Park, Kwiyeom Yoon, Eunji Hong, Min Woo Kim, Min Gi Kang, Seiya Mizuno, Hye Jin Kim, Min-Jung Lee, Hee Jae Choi, Jin Sun Heo, Jin Beom Bae, Haein An, Naim Park, Hyeyeon Park, Pyunggang Kim, Minjung Son, Kyoungwha Pang, Je Yeun Park, Satoru Takahashi, Yong Jung Kwon, Dong-Woo Kang, Seong-Jin Kim","doi":"10.1038/s41413-025-00419-y","DOIUrl":"https://doi.org/10.1038/s41413-025-00419-y","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and abnormal osteoclast activation, leading to bone destruction. We previously demonstrated that the large extracellular loop (LEL) of Tm4sf19 is important for its function in osteoclast differentiation, and LEL-Fc, a competitive inhibitor of Tm4sf19, effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis. This study aimed to investigate the role of Tm4sf19 in RA, an inflammatory and abnormal osteoclast disease, using a mouse model of collagen-induced arthritis (CIA). Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium, and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group. Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model, reducing the CIA score, swelling, inflammation, cartilage damage, and bone damage. Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages. LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2, but also the interaction between TLR4 and MD2. μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice. Taken together, these findings suggest that LEL-Fc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"26 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143678082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-19 DOI: 10.1038/s41413-025-00405-4

Jiawei Lu, Qi He, Huan Wang, Lutian Yao, Michael Duffy, Hanli Guo, Corben Braun, Yilu Zhou, Qiushi Liang, Yuewei Lin, Shovik Bandyopadhyay, Kai Tan, Yongwen Choi, X. Sherry Liu, Ling Qin

{"title":"Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice","authors":"Jiawei Lu, Qi He, Huan Wang, Lutian Yao, Michael Duffy, Hanli Guo, Corben Braun, Yilu Zhou, Qiushi Liang, Yuewei Lin, Shovik Bandyopadhyay, Kai Tan, Yongwen Choi, X. Sherry Liu, Ling Qin","doi":"10.1038/s41413-025-00405-4","DOIUrl":"https://doi.org/10.1038/s41413-025-00405-4","url":null,"abstract":"Bone resorption by osteoclasts is a critical step in bone remodeling, a process important for maintaining bone homeostasis and repairing injured bone. We previously identified a bone marrow mesenchymal subpopulation, marrow adipogenic lineage precursors (MALPs), and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre. To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone, we generated inducible reporter mice (Adipoq-CreER Tomato) and RANKL deficient mice (Adipoq-CreER RANKLflox/flox, iCKO). Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+ cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation. In situ hybridization showed that RANKL mRNA is only detected in MALPs, but not in osteogenic cells. RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone. Ovariectomy (OVX) induced trabecular bone loss at both sites. RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass. Furthermore, bone healing after drill-hole injury was delayed in iCKO mice. Together, our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis, postmenopausal bone loss, and injury repair.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"183 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bone-brain interaction: mechanisms and potential intervention strategies of biomaterials 骨脑相互作用：生物材料的机制和潜在干预策略

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-17 DOI: 10.1038/s41413-025-00404-5

Jiaze Yu, Luli Ji, Yongxian Liu, Xiaogang Wang, Jing Wang, Changsheng Liu

{"title":"Bone-brain interaction: mechanisms and potential intervention strategies of biomaterials","authors":"Jiaze Yu, Luli Ji, Yongxian Liu, Xiaogang Wang, Jing Wang, Changsheng Liu","doi":"10.1038/s41413-025-00404-5","DOIUrl":"https://doi.org/10.1038/s41413-025-00404-5","url":null,"abstract":"Following the discovery of bone as an endocrine organ with systemic influence, bone-brain interaction has emerged as a research hotspot, unveiling complex bidirectional communication between bone and brain. Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways, yet there is a dearth of systematic reviews in this area. This review comprehensively examines interactions across three key areas: the influence of bone-derived factors on brain function, the effects of brain-related diseases or injuries (BRDI) on bone health, and the concept of skeletal interoception. Additionally, the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms, aiming to facilitate bone-brain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases. Notably, the integration of artificial intelligence (AI) in biomaterial design is highlighted, showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies. In conclusion, this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice. These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain, underscoring the potential of interdisciplinary approaches in enhancing human health.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"55 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Organelle-tuning condition robustly fabricates energetic mitochondria for cartilage regeneration 细胞器调谐条件为软骨再生强力制造高能线粒体

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-17 DOI: 10.1038/s41413-025-00411-6

Xuri Chen, Yunting Zhou, Wenyu Yao, Chenlu Gao, Zhuomin Sha, Junzhi Yi, Jiasheng Wang, Xindi Liu, Chenjie Dai, Yi Zhang, Zhonglin Wu, Xudong Yao, Jing Zhou, Hua Liu, Yishan Chen, Hongwei Ouyang

{"title":"Organelle-tuning condition robustly fabricates energetic mitochondria for cartilage regeneration","authors":"Xuri Chen, Yunting Zhou, Wenyu Yao, Chenlu Gao, Zhuomin Sha, Junzhi Yi, Jiasheng Wang, Xindi Liu, Chenjie Dai, Yi Zhang, Zhonglin Wu, Xudong Yao, Jing Zhou, Hua Liu, Yishan Chen, Hongwei Ouyang","doi":"10.1038/s41413-025-00411-6","DOIUrl":"https://doi.org/10.1038/s41413-025-00411-6","url":null,"abstract":"Mitochondria are vital organelles whose impairment leads to numerous metabolic disorders. Mitochondrial transplantation serves as a promising clinical therapy. However, its widespread application is hindered by the limited availability of healthy mitochondria, with the dose required reaching up to 109 mitochondria per injection/patient. This necessitates sustainable and tractable approaches for producing high-quality human mitochondria. In this study, we demonstrated a highly efficient mitochondria-producing strategy by manipulating mitobiogenesis and tuning organelle balance in human mesenchymal stem cells (MSCs). Utilizing an optimized culture medium (mito-condition) developed from our established formula, we achieved an 854-fold increase in mitochondria production compared to normal MSC culture within 15 days. These mitochondria were not only significantly expanded but also exhibited superior function both before and after isolation, with ATP production levels reaching 5.71 times that of normal mitochondria. Mechanistically, we revealed activation of the AMPK pathway and the establishment of a novel cellular state ideal for mitochondrial fabrication, characterized by enhanced proliferation and mitobiogenesis while suppressing other energy-consuming activities. Furthermore, the in vivo function of these mitochondria was validated in the mitotherapy in a mouse osteoarthritis model, resulting in significant cartilage regeneration over a 12-week period. Overall, this study presented a new strategy for the off-the-shelf fabrication of human mitochondria and provided insights into the molecular mechanisms governing organelle synthesis.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"124 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-14 DOI: 10.1038/s41413-025-00413-4

Yaoge Deng, Mingzhuang Hou, Yubin Wu, Yang Liu, Xiaowei Xia, Chenqi Yu, Jianfeng Yu, Huilin Yang, Yijian Zhang, Xuesong Zhu

{"title":"SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch","authors":"Yaoge Deng, Mingzhuang Hou, Yubin Wu, Yang Liu, Xiaowei Xia, Chenqi Yu, Jianfeng Yu, Huilin Yang, Yijian Zhang, Xuesong Zhu","doi":"10.1038/s41413-025-00413-4","DOIUrl":"https://doi.org/10.1038/s41413-025-00413-4","url":null,"abstract":"Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis (OA). However, the underlying mechanisms governing mitochondrial self-renewal and energy production remain elusive. In this study, we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes. Genetically overexpressing PTEN-induced putative kinase 1 (PINK1) protects against cartilage degeneration by removing defective mitochondria. PINK1 knockout aggravated cartilage damage due to impaired mitophagy. SIRT3 directly deacetylated PINK1 to promote mitophagy and cartilage anabolism. Specifically, PINK1 phosphorylated PKM2 at the Ser127 site, preserving its active tetrameric form. This inhibited nuclear translocation and the interaction with β-catenin, resulting in a metabolic shift and increased energy production. Finally, a double-knockout mouse model demonstrated the role of the SIRT3-PINK1-PKM2 axis in safeguarding the structural integrity of articular joints and improving motor functions. Overall, this study provides a novel insight into the regulation of mitochondrial renewal and metabolic switches in OA.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"16 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterizing a new rat model of chronic pain after spine surgery 新型脊柱手术后慢性疼痛大鼠模型的特征描述

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-12 DOI: 10.1038/s41413-025-00408-1

Qichao Wu, Neil C. Ford, Shaoqiu He, Chi Zhang, Xiang Cui, Jing Liu, Xueming Chen, Xu Cao, Yun Guan, Lei Zang

{"title":"Characterizing a new rat model of chronic pain after spine surgery","authors":"Qichao Wu, Neil C. Ford, Shaoqiu He, Chi Zhang, Xiang Cui, Jing Liu, Xueming Chen, Xu Cao, Yun Guan, Lei Zang","doi":"10.1038/s41413-025-00408-1","DOIUrl":"https://doi.org/10.1038/s41413-025-00408-1","url":null,"abstract":"Chronic pain after spine surgery (CPSS) is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40% of patients undergoing lumbar spine surgery. We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures. Step 1: A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion (DRG) and the spinal nerve, a common cause of low back pain (LBP). Step 2: The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw, followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients. The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy. However, rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw, impaired gait, and reduced spontaneous exploration activity, indicating CPSS. Patch clamp recording revealed a significant augmentation in the intrinsic excitability of small-diameter DRG neurons in CPSS rats. Administration of Dermorphin [D-Arg2, Lys4] (1–4) amide (DALDA, 5 mg /kg, i.p.), a peripherally acting mu-opioid receptor (MOR)-preferred agonist, attenuated pain hypersensitivity, capsaicin-induced [Ca2+]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats. Our findings suggest that this new model, which mirrors the nature of CPSS developed in patients, may be useful for future studies of the underlying mechanisms.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"54 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LATS1-modulated ZBTB20 perturbing cartilage matrix homeostasis contributes to early-stage osteoarthritis

IF 12.7 1区医学

Bone Research Pub Date : 2025-03-12 DOI: 10.1038/s41413-025-00414-3

Xue Hao, Jing Zhao, Liyuan Jia, Guangyu Ding, Xiaoju Liang, Fei Su, Shuai Yang, Yating Yang, Jing Fan, Weiping J. Zhang, Liu Yang, Qiang Jie

{"title":"LATS1-modulated ZBTB20 perturbing cartilage matrix homeostasis contributes to early-stage osteoarthritis","authors":"Xue Hao, Jing Zhao, Liyuan Jia, Guangyu Ding, Xiaoju Liang, Fei Su, Shuai Yang, Yating Yang, Jing Fan, Weiping J. Zhang, Liu Yang, Qiang Jie","doi":"10.1038/s41413-025-00414-3","DOIUrl":"https://doi.org/10.1038/s41413-025-00414-3","url":null,"abstract":"Osteoarthritis (OA) is one of the most common degenerative joint diseases in the elderly, increasing in prevalence and posing a substantial socioeconomic challenge, while no disease-modifying treatments available. Better understanding of the early molecular events will benefit the early-stage diagnosis and clinical therapy. Here, we observed the nucleus accumulation of ZBTB20, a member of ZBTB-protein family, in the chondrocytes of early-stage OA. Chondrocytes-specific depletion of Zbtb20 in adult mice attenuated DMM-induced OA progress, restored the balance of extracellular matrix anabolism and catabolism. The NF-κB signaling mediated disturbance of ECM maintenance by ZBTB20 requires its suppression of Pten and consequent PI3K-Akt signaling activation. Furthermore, the subcellular localization of ZBTB20 was modulated by the kinase LATS1. Independent approaches to modulating ZBTB20 via utilizing TRULI and DAPA can restore ECM homeostasis, improving the abnormal behavior and moderating cartilage degeneration. The compounds TRULI and DAPA modulating ZBTB20 may serve as anti-OA drugs.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"49 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0