Bone最新文献

{"title":"Single-cell transcriptomic resolution of osteogenesis during craniofacial morphogenesis","authors":"Erika Hudacova ,&nbsp;Pavel Abaffy ,&nbsp;Mehmet Mahsum Kaplan ,&nbsp;Michaela Krausova ,&nbsp;Mikael Kubista ,&nbsp;Ondrej Machon","doi":"10.1016/j.bone.2024.117297","DOIUrl":"10.1016/j.bone.2024.117297","url":null,"abstract":"<div><div>Craniofacial morphogenesis depends on complex cell fate decisions during the differentiation of post-migratory cranial neural crest cells. Molecular mechanisms of cell differentiation of mesenchymal cells to developing bones, cartilage, teeth, tongue, and other craniofacial tissues are still poorly understood. We performed single-cell transcriptomic analysis of craniofacial mesenchymal cells derived from cranial NCCs in mouse embryo. Using FACS sorting of Wnt1-Cre2 progeny, we carefully mapped the cell heterogeneity in the craniofacial region during the initial stages of cartilage and bone formation. Transcriptomic data and in vivo validations identified molecular determinants of major cell populations involved in the development of lower and upper jaw, teeth, tongue, dermis, or periocular mesenchyme. Single-cell transcriptomic analysis of <em>Meis2</em>-deficient mice revealed critical gene expression differences, including increased osteogenic and cell adhesion markers. This leads to affected mesenchymal cell differentiation and increased ossification, resulting in impaired bone, cartilage, and tongue formation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117297"},"PeriodicalIF":3.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514631","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":"Cardiovascular risk assessment for osteoporosis patients considering Romosozumab","authors":"F. Macrae ,&nbsp;E.M. Clark ,&nbsp;K. Walsh ,&nbsp;S.-J. Bailey ,&nbsp;M. Roy ,&nbsp;S. Hardcastle ,&nbsp;C. Cockill ,&nbsp;J.H. Tobias ,&nbsp;B.G. Faber","doi":"10.1016/j.bone.2024.117305","DOIUrl":"10.1016/j.bone.2024.117305","url":null,"abstract":"<div><div>Cardiovascular risk scoaring tools are suitable for but not interchangable within the osteoporosis clinic.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117305"},"PeriodicalIF":3.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514617","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":"Imminent risk of the first and second recurrent osteoporotic fractures in South Korea","authors":"Miryoung Kim ,&nbsp;Hyun-jin Han ,&nbsp;Donghyun Pyun ,&nbsp;Eyoung Wang ,&nbsp;Min Ji Kim ,&nbsp;Hae Sun Suh","doi":"10.1016/j.bone.2024.117286","DOIUrl":"10.1016/j.bone.2024.117286","url":null,"abstract":"<div><h3>Background</h3><div>A history of fractures increases the likelihood of experiencing subsequent and secondary fractures. To prevent further fractures, global guidelines recommend aggressive proactive treatment with medication for patients at an imminent risk of osteoporotic fracture (OF), which is defined as a high likelihood of experiencing subsequent fractures in the near future. However, there is a lack of research focusing on patients with imminent risk of OFs in South Korea. Hence, this study aimed to evaluate the imminent risk of the first and second recurrent OFs among patients with OF in South Korea.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis using the comprehensive Health Insurance Review and Assessment database, which encompasses the entire population of Korea from 2012 to 2017. The study focused on eligible patients aged 55 years and older who experienced an OF in 2013, including fractures in the hip/femur, vertebral, humerus, radius, tibia/fibula, and ankle regions. The first OF occurring in 2013 was considered the index OF. To ensure that the index fracture was the index OFs, we excluded patients who had any OF within 1 year before their index OF. We assessed the incidence of the first recurrent OF within 2 years after the index OF, and the second recurrent OF within 2 years after the occurrence of the first recurrent OF. Additionally, we estimated the risks of experiencing the first and second recurrent OFs according to age and sex using multi-variable Cox proportional hazard regression analysis.</div></div><div><h3>Results</h3><div>Approximately 17 % of patients with an index OF had the first recurrent OF within 2 years after the index OF. Of those with a first recurrent OF, 28 % experienced a second recurrent OF within 2 years after the first recurrent OF. The two-year incidence rate of the first recurrent OF was 9.6 per 100 person-years (95 % confidence interval [CI], 9.6–9.7). The two-year incidence rate of the second recurrent OF was 22.0 per 100 person-years (95 % CI, 21.6–22.4), which is higher than that of the first recurrent OF. Females had a 31 % higher risk of the first recurrent OF (hazard ratio [HR] = 1.31; 95 % CI, 1.20–1.43) and a 43 % higher risk of the second recurrent OF than males (HR = 1.43; 95 % CI, 1.35–1.51).</div></div><div><h3>Conclusions</h3><div>In Korea, the imminent risk of a second recurrent OF was higher than that of a first recurrent OF. Consequently, given the elevated risk of subsequent fractures with the number of OFs experienced, a more targeted approach to treatment is recommended for patients with a first recurrent OF considering the risk of subsequent OF.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117286"},"PeriodicalIF":3.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514618","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":"Role and mechanism of Actein on condylar bone metabolism in APOE deletion-induced osteoporotic mice","authors":"Linyi Zhou ,&nbsp;Yuqian Li ,&nbsp;Jinjin Ma ,&nbsp;Qi Zhang ,&nbsp;Shuhui Tang ,&nbsp;Kaiao Zou ,&nbsp;Qinghe Zeng ,&nbsp;Haipeng Huang ,&nbsp;Hongting Jin ,&nbsp;Qiaoyan Zhang ,&nbsp;Jianying Feng","doi":"10.1016/j.bone.2024.117304","DOIUrl":"10.1016/j.bone.2024.117304","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the effects of Actein from Cimicifugae Rhizoma on condylar bone and cartilage in <em>APOE</em> deletion-induced osteoporotic mice, and to preliminarily explore the underlying mechanism.</div></div><div><h3>Methods</h3><div>Sixty 8-week-old female mice were used, which underwent <em>APOE</em>^−/− and ovariectomy procedures, followed by oral administration of Actein (15 mg/kg) and Atorvastatin Calcium (AC, 3 mg/kg) for eight weeks. Body weight, uterine weight, and systemic indexes related to bone metabolism and lipid metabolism were assessed in each group. Changes in condylar bone histomorphometric parameters were evaluated using Micro-CT. Morphological changes in the condyle were observed with Hematoxylin-Eosin (H&amp;E), Safranin O/Fast Green, and Alcian Blue Hematoxylin/Orange G (ABH/OG) staining, with OARSI pathology scoring performed. Sirius red staining and immunofluorescence were used to determine the expression levels of Collagen I (Col I) and Collagen III (Col III) in bone matrix, and Col II in cartilage matrix. Immunohistochemistry assessed the relative expression levels of ALP and proteins associated with the Wnt/β-catenin/RUNX2 signaling pathway.</div></div><div><h3>Results</h3><div><em>APOE</em>^−/− exacerbates ovariectomy -induced osteoporosis (OP) in condylar of mice. Actein and AC significantly reversed OP, improved bone mineral density (BMD), increased bone microarchitecture, and restored abnormal calcium and phosphorus metabolism in the blood and urine. Morphologically, <em>APOE</em>^−/− and ovariectomy reduced condylar cartilage thickness, disrupted chondrocyte arrangement, chondrocyte cleavage, and clustered aggregation, resembling osteoarthritis (OA)-like changes. Actein and AC partially restored the disrupted chondrocyte arrangement, smoothed chondrocyte cleavage, and up-regulated the levels of chondrocyte matrix (Col II, aggrecan) and bone matrix (Col III, ALP). Actein reversed the OA process, potentially through the Wnt/β-catenin/RUNX2 signaling pathway.</div></div><div><h3>Conclusion</h3><div><em>APOE</em>^−/− and ovariectomy induced OP, leading to OA-like lesions in condylar of mice. Actein promoted cartilage repair and trabecular bone recovery by increasing extracellular matrix synthesis (Col II, Col III, aggrecan), reversing the OA process, possibly through the Wnt/β-catenin/RUNX2 signaling pathway.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117304"},"PeriodicalIF":3.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514630","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":"AGEs (Advanced Glycation End-products) in bone come of age","authors":"Deepak Vashishth ,&nbsp;Ruban Dhaliwal ,&nbsp;Mishaela Rubin","doi":"10.1016/j.bone.2024.117301","DOIUrl":"10.1016/j.bone.2024.117301","url":null,"abstract":"<div><div>Advanced Glycation End-products (AGEs) are seen in long-lived proteins and were not expected to accumulate in the bone that turnovers and renews itself. Here, we provide a commentary on the contrary, highlighting the <em>Special Issue of AGEs in Bone</em><strong>.</strong> An outcome of hyperglycemia and increased oxidative stress, AGEs form and accumulate by altering the bone resorption and formation processes. Accumulation of various AGEs species in bone increases bone fragility through the stiffening of the collagen network and, potentially, through the changes in collagen-mineral interactions. Evidence from both preclinical and clinical studies is leading to new translational approaches wherein measurement, inhibition, or removal of AGEs show the potential to diagnose, manage, and treat bone fragility associated with multiple conditions and diseases.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117301"},"PeriodicalIF":3.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514615","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":"Downregulation of Krüppel-like factor 15 expression delays endochondral bone ossification during fracture healing","authors":"Shotaro Tachibana ,&nbsp;Shinya Hayashi ,&nbsp;Kemmei Ikuta ,&nbsp;Kensuke Anjiki ,&nbsp;Yuma Onoi ,&nbsp;Yoshihito Suda ,&nbsp;Kensuke Wada ,&nbsp;Takuma Maeda ,&nbsp;Akira Saito ,&nbsp;Masanori Tsubosaka ,&nbsp;Tomoyuki Kamenaga ,&nbsp;Yuichi Kuroda ,&nbsp;Naoki Nakano ,&nbsp;Tomoyuki Matsumoto ,&nbsp;Tetsuya Hosooka ,&nbsp;Wataru Ogawa ,&nbsp;Ryosuke Kuroda","doi":"10.1016/j.bone.2024.117302","DOIUrl":"10.1016/j.bone.2024.117302","url":null,"abstract":"<div><h3>Objective</h3><div>The role of Krüppel-like zinc finger transcription factor 15 (KLF15) in endochondral ossification during fracture healing remains unexplored. In this study, we aimed to elucidate the impact of KLF15 in a mouse model of tibial transverse fracture.</div></div><div><h3>Methods</h3><div>We created tamoxifen-inducible, cartilage-specific KLF15 knockout mice (KLF15 KO). KLF15 ^fl/fl Col2-CreERT mice from the same litters as the KLF15 KO mice, but not treated with 4-hydroxytamoxifen, were used as controls (CT). At 10 weeks, male KLF15 KO and CT mice underwent tibial fracture followed by intramedullary nailing. Both groups were administered tamoxifen at days 0, 3, and 7 after surgery. The tibiae were harvested on post-surgery days 7, 10, and 14 for radiological assessment using micro-computed tomography. Histological staining (Safranin-O) and immunohistochemistry for KLF15, SOX9, Indian hedgehog (IHH), RUNX2, and Osterix were performed. Additionally, cartilage from mouse fetus was cultured for qRT-PCR and western blot analyses of KLF15, SOX9, IHH, Col2, RUNX2, Osterix, TGF-β, SMAD3, and phosphor-SMAD3.</div></div><div><h3>Results</h3><div>The radiological assessment revealed that immature callus formation was delayed in KLF15 KO, compared with that in CT, peaking on day 14 compared with that on day 10 in CT. KLF15 KO mice exhibited delayed fracture healing and reduced Safranin-O staining at days 7 and 10 post-surgery. The ratio of cells positive for KLF15 and SOX9 was significantly lower in KLF15 KO than in CT, whereas the ratios for IHH, RUNX2, and Osterix showed no significant difference. RT-PCR revealed reduced expression of KLF15, SOX9, and COL2, with no significant changes in IHH, Osterix, RUNX2, TGF-β, and SMAD3. Western blot analysis indicated decreased SMAD3 phosphorylation in KLF15 KO mice.</div></div><div><h3>Conclusion</h3><div>KLF15 regulates SOX9 via the TGF-β-SMAD3-SOX9 pathway, independent of IHH, in endochondral ossification. The KLF15 deficiency decreases SOX9 expression through reduced SMAD3 phosphorylation, subsequently delaying fracture healing.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117302"},"PeriodicalIF":3.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514633","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":"Dynamic control of mTORC1 facilitates bone healing in mice","authors":"Delong Li ,&nbsp;Daozhang Cai ,&nbsp;Denghui Xie ,&nbsp;Liang Wang ,&nbsp;Yan Zhang ,&nbsp;Guangfeng Ruan ,&nbsp;Qun Zhang ,&nbsp;Bo Yan ,&nbsp;Haiyan Zhang ,&nbsp;Pinglin Lai ,&nbsp;Zhengquan Liao ,&nbsp;Yu Jiang ,&nbsp;Dianbo Yu ,&nbsp;Changhai Ding ,&nbsp;Chengliang Yang","doi":"10.1016/j.bone.2024.117285","DOIUrl":"10.1016/j.bone.2024.117285","url":null,"abstract":"<div><div>Bone healing requires well-orchestrated sequential actions of osteoblasts and osteoclasts. Previous studies have demonstrated that the mechanistic target of rapamycin complex 1 (mTORC1) plays a critical role in the metabolism of osteoblasts and osteoclasts. However, the role of mTORC1 in bone healing remains unclear. Here, we showed that a dynamic change in mTORC1 activity during the process was essential for proper healing and can be harnessed therapeutically for treatment of bone fractures. Low mTORC1 activity induced by osteoblastic <em>Raptor</em> knockout or rapamycin treatment promoted osteoblast-mediated osteogenesis, thus leading to better bone formation and shorter bone union time. Rapamycin treatment <em>in vitro</em> also revealed that low mTORC1 activity enhanced osteoblast differentiation and maturation. However, rapamycin treatment affected the recruitment of osteoclasts to new bone sites, thus resulting in delayed callus absorption in bone marrow cavity. Mechanistically, decreased mTORC1 activity inhibited the recruitment of osteoclast progenitor cells to healing sites through a decrease in osteoblastic expression of monocyte chemoattractant protein-1, thus inhibiting osteoclast-mediated remodeling. Therefore, normal mTORC1 activity was necessary for bone remodeling stage. Furthermore, through the use of sustained-release materials at the bone defect, we confirmed that localized application of rapamycin in early stages accelerated bone healing without affecting bone remodeling. Together, these findings revealed that the activity of mTORC1 continually changed during bone healing, and staged rapamycin treatment could be used to promote bone healing.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117285"},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483026","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":"OMIBONE: Omics-driven computer model of bone regeneration for personalized treatment","authors":"Mahdi Jaber ,&nbsp;Johannes Schmidt ,&nbsp;Stefan Kalkhof ,&nbsp;Louis Gerstenfeld ,&nbsp;Georg N. Duda ,&nbsp;Sara Checa","doi":"10.1016/j.bone.2024.117288","DOIUrl":"10.1016/j.bone.2024.117288","url":null,"abstract":"<div><div>Treatment of bone fractures are standardized according to the AO classification, which mainly refers to the mechanical stabilization required in a given situation but neglect individual differences due to patient's healing potential or accompanying diseases. Specially in elderly or immune-compromised patients, the complexity of individual constrains on a biological as well as mechanical level are hard to account for. Here, we introduce a novel framework that allows to predict bone regeneration outcome using combined proteomic and mechanical analyses in a computer model. The framework uses Ingenuity Pathway Analysis (IPA) software to link protein changes to alterations in biological processes and integrates these in an Agent-Based Model (ABM) of bone regeneration. This combined framework allows to predict bone formation and the potential of an individual to heal a given fracture setting. The performance of the framework was evaluated by replicating the experimental setup of a mouse femur fracture stabilized with an intramedullary pin. The model was informed by serum derived proteomics data. The tissue formation patterns were compared against experimental data based on x-ray and histology images. The results indicate the framework potential in predicting an individual's bone formation potential and hold promise as a concept to enable personalized bone healing predictions for a chosen fracture fixation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117288"},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483028","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":"Mechanical complications and revision following total joint arthroplasty in acromegalic patients: A nationwide US-based study","authors":"Amirhossein Ghaseminejad-Raeini ,&nbsp;Amir Human Hoveidaei ,&nbsp;Amir Hekmat Hamrahian ,&nbsp;Ashkan Bahrami ,&nbsp;Sina Esmaeili ,&nbsp;Shayan Eghdami ,&nbsp;Basilia Onyinyechukwu Nwankwo ,&nbsp;Mohammad Saeid Khonji ,&nbsp;Janet D. Conway","doi":"10.1016/j.bone.2024.117296","DOIUrl":"10.1016/j.bone.2024.117296","url":null,"abstract":"<div><h3>Background</h3><div>Acromegaly is associated with significant osteoarthritis (OA) and increased risk of vertebral and hip fractures. There is limited data on total joint arthroplasty (TJA) outcomes in patients with acromegaly.</div></div><div><h3>Methods</h3><div>In this retrospective study, we identified patients with acromegaly who underwent total hip arthroplasty (THA), total knee arthroplasty (TKA), and total shoulder arthroplasty (TSA) between 2010 and 2022 using the PearlDiver national database. Patients with a prior history of osteoporosis and follow-up duration of less than one year were excluded. Non-acromegalic control groups were selected through matching based on confounding factors. We compared all-cause revision and implant-related complications between the groups using R software integrated with the PearlDiver database.</div></div><div><h3>Results</h3><div>We identified 1440 patients with acromegaly: 665 underwent THA, 618 underwent TKA, and 157 underwent TSA. Compared to the control group (2634 THA, 2445 TKA, and 600 TSA), there was no significant association with post-op revision following THA (OR(1-year) = 0.76[0.42–1.28], OR(5-year) = 0.68[0.42–1.06]), TKA (OR(1-year) = 0.89[0.48–1.55], OR(5-year) = 0.78[0.49–1.17]), and TSA (OR(1-year) = 0.19[0.02–1.40], OR(5-year) = 0.32[0.10–1.07]). Additionally, the risk of mechanical complications did not significantly increase in patients with acromegaly, either one year or five years post-operation.</div></div><div><h3>Conclusion</h3><div>The study showed no significant increase in risk of revisions or mechanical complications in patients with acromegaly compared to controls. These findings bridge an important gap in the understanding of post-arthroplasty complications in patients with acromegaly and offer valuable insights into surgical expectations.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117296"},"PeriodicalIF":3.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483032","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":"Mechanotransduction pathways regulating YAP nuclear translocation under Yoda1 and vibration in osteocytes","authors":"Chun-Yu Lin ,&nbsp;Amel Sassi ,&nbsp;Yuning Wu ,&nbsp;Kimberly Seaman ,&nbsp;Wentian Tang ,&nbsp;Xin Song ,&nbsp;Raphael Bienenstock ,&nbsp;Hiroki Yokota ,&nbsp;Yu Sun ,&nbsp;Fei Geng ,&nbsp;Liyun Wang ,&nbsp;Lidan You","doi":"10.1016/j.bone.2024.117283","DOIUrl":"10.1016/j.bone.2024.117283","url":null,"abstract":"<div><div>Yes-associated protein (YAP) is a mechanosensitive protein crucial for bone remodeling. Although research has identified pathways and components involved in YAP regulation, the precise mechanisms of its localization during Piezo1 activation or vibration remain unclear. Piezo1, a mechanosensitive ion channel, allows calcium ions to flow into cells upon activation. Recent studies suggest that combining Yoda1, a Piezo1 activator, with low-magnitude high-frequency (LMHF) vibration (&gt;30 Hz, &lt;1 g acceleration) enhances YAP nuclear translocation. This combination potentially improves the mechanoresponse and therapeutic efficacy of LMHF vibration in bone cells. This study aims to elucidate how Yoda1 and LMHF vibration regulate mechanosensitive structures and pathways, leading to YAP nuclear translocation in MLO-Y4 osteocyte like cells. We investigated the roles of the cytoskeleton and nuclear envelope (NE) in YAP activation under combined LMHF vibration and Yoda1 treatments. Additionally, we analyzed differentially expressed genes (DEGs) in MLO-Y4 cells subjected to these treatments and in Piezo1 knockdown MLO-Y4 cells exposed to vibration. Our findings indicated that increased YAP nuclear translocation with combined treatment may result from the distinct effects of Yoda1 and vibration. Specifically, Yoda1 influenced YAP through mechanisms involving actin and NE dynamics, while LMHF vibration may modulate YAP via the interleukin 6 (IL6)/signal transducer and activator of transcription 3 (STAT3) axis. This study provides new insights and potential therapeutic targets for osteocyte-related pathologies.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117283"},"PeriodicalIF":3.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483027","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}