Bone最新文献

{"title":"RANKL-derived peptide MHP1-AcN attenuates ovariectomy-induced osteoporosis by targeting RANK and TNFR1 in mice","authors":"Takuya Kurihara ,&nbsp;Munehisa Shimamura ,&nbsp;Yuki Etani ,&nbsp;Takaaki Noguchi ,&nbsp;Yuji Fukuda ,&nbsp;Nagahiro Ochiai ,&nbsp;Atsushi Goshima ,&nbsp;Taihei Miura ,&nbsp;Makoto Hirao ,&nbsp;Atsushi Sugimoto ,&nbsp;Nan Ju ,&nbsp;Satoshi Yamakawa ,&nbsp;Takashi Kanamoto ,&nbsp;Ken Nakata ,&nbsp;Seiji Okada ,&nbsp;Kosuke Ebina","doi":"10.1016/j.bone.2025.117440","DOIUrl":"10.1016/j.bone.2025.117440","url":null,"abstract":"<div><h3>Purpose</h3><div>Estrogen deficiency following menopause increases receptor activator of nuclear factor-kappa B ligand (RANKL) expression in osteoblasts, thereby promoting osteoclast differentiation, and enhances T cell-derived tumor necrosis factor-alpha (TNFα) production, which induces sclerostin expression in osteocytes, thereby inhibiting bone formation. This study aimed to develop a novel uncoupling therapeutic agent for osteoporosis.</div></div><div><h3>Methods</h3><div>We developed microglial healing peptide 1 with N-terminal acetylation and C-terminal amidation (MHP1-AcN), a modified RANKL peptide with N-terminal acetylation and C-terminal amidation lacking the osteoclast activating CD loop. Given the structural similarities of RANK and TNF receptor 1 (TNFR1), we hypothesized that MHP1-AcN could inhibit both the RANKL–RANK and TNFα–TNFR1 pathways to address the pathophysiology of osteoporosis, as evaluated in vitro and in vivo using an ovariectomized mouse model.</div></div><div><h3>Results</h3><div>In ovariectomized mice, MHP1-AcN inhibited osteoclastogenesis, reduced osteocytic sclerostin expression, prevented bone loss, and improved the femoral cancellous and cortical bone microarchitecture. Unlike anti-RANKL antibody, MHP1-AcN considerably preserved bone formation by osteoblasts and enhanced bone strength, as evidenced by increases in energy absorption capacity. In vitro, MHP1-AcN bound to both RANK and TNFR1, suppressing osteoclast activity via the RANKL–RANK pathway and reducing sclerostin expression through the TNFα–TNFR1–nuclear factor-kappa B pathway. MHP1-AcN did not affect osteoblast proliferation and differentiation or RANKL expression.</div></div><div><h3>Conclusion</h3><div>MHP1-AcN effectively inhibits osteoclastogenesis and sclerostin-mediated suppression of bone formation while considerably preserving osteoblast function. These findings suggest that MHP1-AcN, which targets dual pathways critical for bone homeostasis, is a promising uncoupling therapeutic agent for osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117440"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528702","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":"Unraveling the dynamics of osteoblast differentiation in MC3T3-E1 cells: Transcriptomic insights into matrix mineralization and cell proliferation","authors":"Heein Yoon ,&nbsp;Seung Gwa Park ,&nbsp;Hye-Rim Shin ,&nbsp;Ki-Tae Kim ,&nbsp;Young-Dan Cho ,&nbsp;Jae-I Moon ,&nbsp;Woo-Jin Kim ,&nbsp;Hyun-Mo Ryoo","doi":"10.1016/j.bone.2025.117442","DOIUrl":"10.1016/j.bone.2025.117442","url":null,"abstract":"<div><div>Unraveling the intricacies of osteoblast differentiation is crucial for advancing our comprehension of bone biology. This study investigated the complicated molecular events orchestrating osteoblast differentiation in MC3T3-E1 cells, a well-established in vitro culture model. Employing longitudinal RNA-sequencing analysis, we explored transcriptomic changes at the pivotal time points of 0, 1, 4, 7, 10, 14, and 21 days and categorized osteogenic differentiation into proliferation, matrix maturation, and mineralization stages. Notably, we observed a simultaneous increase in matrix mineralization and cell proliferation during the mineralization stage, accompanied by a positive correlation between proliferation-associated genes and those enriched in ossification. Additionally, we identified the presence of proliferating cells over the mineralizing matrix layers. These results could serve as a model for understanding the principles by which bone lining cells are formed on the calcified bone matrix and the mechanism by which new osteoblasts are recruited during the bone remodeling process.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117442"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528704","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":"Human cortical bone intrinsic permeability distribution based on 3D canalicular morphology","authors":"Remy Gauthier ,&nbsp;Hélène Follet ,&nbsp;Cécile Olivier ,&nbsp;Thibault Lemaire ,&nbsp;David Mitton ,&nbsp;Francoise Peyrin","doi":"10.1016/j.bone.2025.117441","DOIUrl":"10.1016/j.bone.2025.117441","url":null,"abstract":"<div><div>Bone permeability is a key parameter that drives osteocyte-based mechanobiological modelling and remodelling. While previous experimental and numerical studies have estimated bone permeability based on the morphology of the lacuno-canalicular network, these studies often relied on simplified geometries. In the current study, bone permeability was characterized using more realistic canalicular geometry for the morphological data. Bone samples harvested from 27 human femoral bones were investigated using synchrotron radiation-based nano-computed tomography with a voxel size of 100 nm. After segmenting the canaliculi and lacunae, each canaliculus was investigated individually by applying a distance map and watershed algorithms. Bone permeability based on canalicular morphology was then assessed using the Kozeny relation, which defines the permeability of a porous medium with capillary-like pores. An averaged intrinsic permeability value of 8.8 10⁻¹⁸ m² was obtained. It should be noted that this study considered an empty canalicular network, however <em>in vivo</em>, both cellular and peri-cellular matrices decrease space for interstitial fluid flow and thus permeability. Furthermore, a voxel size of 100 nm does not allow for the detection of smaller canaliculi, which may also modify average permeability. With the current data set and the analytic process applied, the results showed a heterogeneous permeability distribution within bone tissue, both when comparing osteonal and interstitial tissues and within an individual osteon. A difference was observed between male and female samples, and permeability appeared to significantly decrease with age. Finally, a significant correlation was found between permeability and canalicular length density, defined as canalicular length per unit bone volume. This study proposes a new form of the Kozeny law to express bone canalicular permeability as a proportional relationship with the canalicular length density. Importantly, this parameter can be directly quantified through confocal fluorescence microcopy, which is more convenient than synchrotron radiation-based nano-computed tomography. In conclusion, the current study confirms that confocal microscopy can be serve as a reliable tool to estimate bone permeability. However, the permeability values calculated here are solely based on canalicular morphology and do not consider cellular and peri-cellular intra-canalicular features.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117441"},"PeriodicalIF":3.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527203","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":"Bone proliferation in osteoporotic experimental animals using alginate-pullulan-bioactive glass‑gold nanoparticles composite","authors":"Andreea Niculina Aștilean (Pertea) ,&nbsp;Alexandra Dreancă ,&nbsp;Sidonia Gog-Bogdan ,&nbsp;Bogdan Sevastre ,&nbsp;Andrei Ungur ,&nbsp;Andrada Negoescu ,&nbsp;Marian Taulescu ,&nbsp;Oana Rotar ,&nbsp;Maximilian Dindelegan ,&nbsp;Luciana-Mădălina Gherman ,&nbsp;Klara Magyari ,&nbsp;Liviu Oana","doi":"10.1016/j.bone.2025.117439","DOIUrl":"10.1016/j.bone.2025.117439","url":null,"abstract":"<div><div>In the present study, scaffold composites based on alginate-pullulan-bioactive glass‑gold nanoparticles were orthotopically implanted in an experimental model of delayed bone union, in rats, given by a metabolic pathology, namely osteoporosis. Differences between treated and untreated groups were observed and the efficacy of our biomaterial was evaluated by applying micro-CT imaging, together with histological evaluation of the osteoporotic animals with sub-critical bone defects, at 30 and 60 days. Osteoporosis was successfully induced by ovariectomy in 9-month-old rats, confirmed by micro-CT and histopathological analysis. A secondary complication from a cortical bone defect was further induced to study bone proliferation in such a delayed environment. The studied composite presents osteointegration and angiogenesis properties at 60 days post-implantation in the osteoporotic animals. These results are given by the micro-CT analysis in which higher bone mineral density and bone volume fraction were observed, alongside histopathology, stating a lack of tissue necrosis and inflammatory reaction and the presence of new woven islands within and around the implanted biomaterial. This is the first endeavor to treat cortical bone defects in osteoporotic animals using scaffold biopolymers containing bioactive glass‑gold nanoparticles instead of cement.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117439"},"PeriodicalIF":3.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534142","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":"Automatic phantom-less calibration of routine CT scans for the evaluation of osteoporosis and hip fracture risk","authors":"Wen Li ,&nbsp;Yuanzhi Weng ,&nbsp;Renfei Zong ,&nbsp;Miao Wei ,&nbsp;Chen Zheng ,&nbsp;Minghao Wu ,&nbsp;Wenqin Zhou ,&nbsp;Jiayi Pu ,&nbsp;William Lu ,&nbsp;Fajin Lv","doi":"10.1016/j.bone.2025.117431","DOIUrl":"10.1016/j.bone.2025.117431","url":null,"abstract":"<div><div>Background/Purpose.</div><div>The diagnosis of osteoporosis remains a paramount concern for orthopedic surgeons worldwide. We aim to (1) evaluate the efficacy of automatic phantom-less quantitative computed tomography (PL-QCT) in diagnosing osteoporosis and (2) investigate its clinical value in predicting hip fracture risk.</div></div><div><h3>Methods</h3><div>A cohort of 705 patients was included in the study. Hip CT scans from 310 patients and spinal CT scans from 315 patients were analyzed using automatic PL-QCT. The consistency of bone mineral density (BMD) measurement obtained by dual-energy X-ray absorptiometry (DXA), phantom-based QCT (PB-QCT), and automatic PL-QCT was examined through linear regression analysis and Bland-Altman plots. The ability of automatic PL-QCT to predict osteoporosis and hip fracture risk was assessed using ROC analysis.</div></div><div><h3>Results</h3><div>Linear regression and Bland-Altman plots demonstrated a high level of agreement between BMD measurements from PL-QCT and those from hip DXA and lumbar PB-QCT. The AUC values for PL-QCT and PB-QCT in diagnosing osteoporosis were 0.903 (95 % CI 0.852–0.955) and 0.900 (95 % CI 0.847–0.953). The AUC values for predicting hip fracture risk, based on femoral neck BMD measured by PL-QCT and DXA, were 0.869 (95 % CI 0.823–0.915) and 0.831(95 % CI 0.778–0.885), respectively. When the femoral neck BMD was combined with the percentage of inter-muscular adipose tissue area, the AUC increased to 0.929 (95 % CI 0.897–0.961).</div></div><div><h3>Conclusion</h3><div>Automatic PL-QCT has shown superior performance in predicting hip fracture risk compared to DXA. Furthermore, the novel PL-QCT demonstrates comparable predictive efficacy to that of PB-QCT, suggesting its potential as a valuable tool in clinical practice.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117431"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511712","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":"Use of double-echo ultrashort echo time magnetic resonance imaging to assess proximal femoral cortical bone changes in axial spondyloarthritis","authors":"Yitong Li,&nbsp;Bowen Hou,&nbsp;Yao Zhang,&nbsp;Yi Wang,&nbsp;Yongqiang Chu,&nbsp;Jing Zhang,&nbsp;Xiaoming Li","doi":"10.1016/j.bone.2025.117430","DOIUrl":"10.1016/j.bone.2025.117430","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;We quantitatively evaluated proximal femoral cortical bone changes associated with generalized bone loss in axial spondyloarthritis (axSpA) patients using double-echo ultrashort echo time (UTE) MRI. To achieve non-radiation, clinically available visualization of cortical microstructural deterioration in the proximal femur of axSpA and to determine the factors influencing it.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Patients with axSpA (&lt;em&gt;n&lt;/em&gt; = 83) and age- and sex-matched healthy controls (&lt;em&gt;n&lt;/em&gt; = 61) were recruited and underwent double-echo UTE MR scan of the nondominant proximal femur. Porosity index (PI) and cortical bone thickness (CbTh) were measured by two radiologists and their average measurements were used for subsequent analyses. Additionally, demographic characteristics of all subjects and disease-specific characteristics of axSpA patients were recorded. Proximal femoral cortical bone PI and CbTh values were compared between axSpA patients and healthy controls using independent samples &lt;em&gt;t&lt;/em&gt;-test. Correlation analyses (Pearson or Spearman or Point-biserial correlation coefficients) were conducted to investigate factors potentially associated with UTE measurements in axSpA patients, and Bonferroni correction was applied at the α = 0.002 level for more stringent correction. Multiple linear regression analyses were performed to further identify influencing factors of UTE measurements with multiple correlated variables.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 72 axSpA patients and 52 healthy control subjects were finally included. Patients and control subjects were comparable in sex, age, and body mass index (BMI). Proximal femoral cortical PI was higher (&lt;em&gt;p&lt;/em&gt; &lt; 0.001) and CbTh was lower (&lt;em&gt;p&lt;/em&gt; &lt; 0.001) in axSpA patients than in healthy controls. Sex (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), BMI (&lt;em&gt;p&lt;/em&gt; = 0.003), disease duration (&lt;em&gt;p&lt;/em&gt; = 0.044), onset age (&lt;em&gt;p&lt;/em&gt; = 0.01), alkaline phosphatase (ALP) (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), radiographic axSpA (r-axSpA) (&lt;em&gt;p&lt;/em&gt; = 0.02), Sacroiliac Joint Structural Score (&lt;em&gt;SSS&lt;/em&gt;)-backfill (&lt;em&gt;p&lt;/em&gt; = 0.03), SSS-ankylosis (&lt;em&gt;p&lt;/em&gt; = 0.01), and nonsteroidal anti-inflammatory drugs (NSAIDs) use (&lt;em&gt;p&lt;/em&gt; = 0.03) were potentially correlated to proximal femoral cortical PI, and among them, sex (&lt;em&gt;p&lt;/em&gt; &lt; 0.001) and BMI (&lt;em&gt;p&lt;/em&gt; = 0.01) were independently associated demographic characteristics, and ALP (&lt;em&gt;p&lt;/em&gt; = 0.02), SSS-backfill (&lt;em&gt;p&lt;/em&gt; = 0.044) and SSS-ankylosis (&lt;em&gt;p&lt;/em&gt; = 0.01) were independently associated disease-specific characteristics, and when all types of variables were considered, sex (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), BMI (&lt;em&gt;p&lt;/em&gt; = 0.016), and SSS-ankylosis (&lt;em&gt;p&lt;/em&gt; = 0.042) were independently associated with PI. BMI (&lt;em&gt;p&lt;/em&gt; = 0.043) and NSAIDs use (&lt;em&gt;p&lt;/em&gt; = 0.041) were potentially negatively associated with CbTh.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Double-echo UTE measurements reve","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117430"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488182","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":"Comment on “Characteristics of patients with very high fracture risk in a community-dwelling geriatric cohort”","authors":"Jian Tong","doi":"10.1016/j.bone.2025.117429","DOIUrl":"10.1016/j.bone.2025.117429","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117429"},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511713","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":"Acute pain trajectories in elderly patients with fragility hip fractures","authors":"Paul Potnuru ,&nbsp;Christina Goehl ,&nbsp;Katherine S. Becker ,&nbsp;Alejandro Juul ,&nbsp;Madison Aycock ,&nbsp;Johanna Blair de Haan ,&nbsp;Sudipta Sen ,&nbsp;Michelle Ge ,&nbsp;Stephen J. Warner ,&nbsp;Nadia Hernandez","doi":"10.1016/j.bone.2025.117428","DOIUrl":"10.1016/j.bone.2025.117428","url":null,"abstract":"<div><h3>Background</h3><div>Pain management for hospitalized elderly patients with fragility hip fractures (FHF) remains challenging. This study aims to distinguish acute pain trajectories in FHF patients that can inform personalized analgesia management.</div></div><div><h3>Methods</h3><div>We conducted a prospective observational study of patients aged 65 and older with FHF at a Level I trauma center. The primary outcome was daily average pain assessed for five days post-injury using the Brief Pain Inventory (BPI). We used group-based trajectory modeling (GBTM) to distinguish acute pain trajectories. Then, factors and secondary outcomes (opioid use and hospital length of stay [LOS]) associated with more severe pain trajectories were identified.</div></div><div><h3>Results</h3><div>We enrolled 100 consecutive patients with FHF between June 2022 and June 2023. We identified three distinct acute pain trajectories: minimal pain, subsiding pain, and persistent pain. Factors associated with more severe pain trajectories included higher initial pain on admission (OR 1.17, 95 % CI 1.02–1.36, <em>P</em> = 0.047), higher BMI (OR 1.15, 95 % CI 1.02–1.29, <em>P</em> = 0.021), and intertrochanteric fracture type (OR = 6.46, 95 % CI 1.49–27.98, <em>P</em> = 0.013). The persistent pain trajectory was significantly associated with 40 % more opioid use (P = 0.01) and a longer LOS (LOS ratio = 1.45, 95 % CI 1.21–1.74, <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Acute pain in FHF patients can be classified into distinct trajectories, providing a basis for personalized pain management. More severe pain trajectories are associated with higher opioid use and longer length of hospital stay.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117428"},"PeriodicalIF":3.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474888","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":"Notch signaling in osteoblast progenitor cells is required for BMP-induced bone formation","authors":"Heather M. Wilson ,&nbsp;Madison A. Buckles ,&nbsp;Parker K. Acevedo ,&nbsp;Christina Capobianco ,&nbsp;Danny M. Nguyen ,&nbsp;Karen Kessell ,&nbsp;Ingrid L. Bergin ,&nbsp;Yadav Wagley ,&nbsp;Ivo Kalajzic ,&nbsp;Kurt D. Hankenson","doi":"10.1016/j.bone.2025.117425","DOIUrl":"10.1016/j.bone.2025.117425","url":null,"abstract":"<div><div>Notch signaling is active during bone formation and prior studies have shown that it is required for both robust intramembranous and endochondral bone regeneration. Particularly, the systemic blockade of Notch signaling has been shown to inhibit BMP-induced bone formation in a murine calvarial defect model. In this study, we genetically disrupted the expression of both the dominant Notch receptor, Jagged-1, and the essential Notch signaling transcription factor Rbpj in osteoblast progenitors during calvarial bone healing. We found that Jagged-1 (and Jagged-2) expression by alpha Smooth Muscle Actin (αSMA) expressing progenitors is required for bone formation. Similarly, we found that Notch transcriptional activity within the αSMA lineage is required for BMP-induced bone regeneration. Inhibition of Notch signaling in the αSMA lineage resulted in decreased osteoblast progenitors, reduced vascularization, and sustained inflammation 10 days post-injury, with enhanced inflammation still present 42 days post-injury. We conclude that Jagged ligand induced Notch signaling within the osteoblast progenitor lineage is therefore required for bone morphogenetic proteins (BMP) induced bone regeneration. Modulation of Notch signaling may represent a new approach to promote bone repair.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"194 ","pages":"Article 117425"},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470231","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":"3D spatial distribution of Sost mRNA and sclerostin protein expression in response to in vivo tibia loading in female mice","authors":"Quentin A. Meslier ,&nbsp;Jacy Hoffmann ,&nbsp;Robert Oehrlein ,&nbsp;Daniel Kurczy ,&nbsp;James R. Monaghan ,&nbsp;Sandra J. Shefelbine","doi":"10.1016/j.bone.2025.117422","DOIUrl":"10.1016/j.bone.2025.117422","url":null,"abstract":"<div><div>Bones adapt to external mechanical loads through a process known as mechanoadaptation. Osteocytes are the bone cells that sense the mechanical environment and initiate a biological response. Investigating the changes in osteocyte molecular expression following mechanical loading has been instrumental in characterizing the regulatory pathways involved in bone adaptation. However, current methods for examining osteocyte molecular expression do not preserve the three-dimensional structure of the bone, which plays a critical role in the mechanical stimuli sensed by the osteocytes and their spatially controlled biological responses.</div><div>In this study, we used WISH-BONE (Whole-mount In Situ Histology of Bone) to investigate the spatial distribution of <em>Sost</em>-mRNA transcripts and its encoded protein, sclerostin, in 3D mouse tibia midshaft following in vivo tibia loading. Our findings showed a decrease in the percentage of <em>Sost</em>-positive osteocytes, after loading, along the posterior-lateral side of the tibia. The number of sclerostin-positive osteocytes were found to significantly decrease at a very specific 2D location of the tibia after loading. However, in 3D, the total number of sclerostin-positive osteocytes was similar between loaded and control legs.</div><div>This work is the first to provide a 3D analysis of <em>Sost</em> and sclerostin distribution in loaded versus contralateral mouse tibia midshafts. It also highlights the importance of the bone region analyzed and the method utilized when interpreting mechanoadaptation results. WISH-BONE represents a powerful tool for further characterization of mechanosensitive genes regulation in bone and holds the potential for advancing the development of new treatments targeting mechanosensitivity-related bone disorders.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"193 ","pages":"Article 117422"},"PeriodicalIF":3.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464892","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}