Journal of Bone and Mineral Research最新文献

{"title":"Recovery of BMD after pregnancy and breastfeeding-a 10-yr prospective observational study of 25-yr-old women.","authors":"Lisa Egund, Linnea Malmgren, Anthony D Woolf, Fiona E McGuigan, Kristina E Akesson","doi":"10.1093/jbmr/zjaf087","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf087","url":null,"abstract":"<p><p>Pregnancy and lactation require large amounts of calcium potentially depleting the young adult bone. This study investigated BMD and fluctuations of BMD resulting from parity and lactation in the PEAK-25 cohort, a prospective observational study of women all aged 25 at inclusion and 35 at follow-up. The analyses use women who were nulliparous at baseline and parous (n = 573) or nulliparous (n = 177) 10-yr later. Parity, regardless of number of pregnancies, had no negative impact, indeed spine BMD at age 35 was higher (2.1%; p = .043). Likewise, BMD did not differ in women who breastfed, were non-lactating or nulliparous. Even the cumulative duration of breastfeeding did not make a difference. Overall, and regardless of parity, in the cohort, by age 35 BMD is already decreasing, with overall losses at femoral neck (∆ - 3.4%) and total hip (∆ - 2.7%); although not spine (∆0.9%). Yet, BMD fluctuations associated with pregnancy, lactation and weaning were seen in the short term. Comparing those pregnant more than 24 m with those less than 24 m prior to DXA, BMD was lowest in women more recently pregnant (FN -2.2%, TH -2.7%). Women pregnant within 12 m had 4% lower TH BMD compared to more than 36 m (p = .054, padj = 0.032). Cumulative duration of breastfeeding was associated with bone loss, particularly beyond 15 mo (FN ∆-4.3%; TH ∆-3.7%) and lower spine BMD accretion. Despite such periods of loss, BMD recovers, evidenced by time-from-weaning to DXA. Women weaning within 6 mo of measurement had lower FN BMD compared to those where the interval was more than 24 mo (6.6% vs 1.7%, p < .001). In conclusion and despite repeated fluctuations in BMD resulting from the physiological demands of multiple pregnancies and periods of breastfeeding, BMD recovers and ultimately doesn't differ from that of identically aged women without children.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525724","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}

{"title":"Early determination of the dorsal-ventral axis in endochondral ossification in mice.","authors":"Sixun Wu, Hirotaka Matsumoto, Jumpei Morita, Mina Yamabe, Azumi Noguchi, Shinsuke Ohba, Noriaki Ono, Yuki Matsushita","doi":"10.1093/jbmr/zjaf086","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf086","url":null,"abstract":"<p><p>Endochondral ossification is a highly coordinated process involving distinct progenitor cell populations within the mesenchymal condensation and subsequent cartilage anlage and perichondrium, all of which drive skeletal formation. Cell type-specific lineage tracing conducted to understand fetal bone development has revealed various fates of early skeletal cells. However, the underlying continuous and precise cellular dynamics of fetal skeletal cells, particularly along the dorsoventral axis, remain unclear. Here, we show that spatiotemporally specific skeletal progenitor cells in the early developmental stage contribute to the dorsal-ventral axis in a manner that is strictly determined during initial developmental stages. Lineage-tracing experiments using Fgfr3-creER and Dlx5-creER lines revealed that Fgfr3+ cells in mesenchymal condensation exclusively contributed to hypertrophic chondrocytes and the dorsal side of the resting and proliferating zones within the cartilage anlage. These cells made dorsal-restricted contributions to skeletal development, including growth plate chondrocytes, trabecular and cortical osteoblasts, and bone marrow stromal cells. Functional ablation of Fgfr3+ cells using the Rosa26iDTA (inducible diphtheria toxin fragment A) allele during the mesenchymal condensation stage caused severe disruption in long bone development, underscoring its indispensable role in initiating skeletal growth. Collectively, these findings suggest that the condensation stage is pivotal for the formation of skeletal progenitors and dorsoventral patterning during bone development. Understanding these mechanisms will provide insight into skeletal growth disorders and therapeutic strategies for bone regeneration.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525720","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}

{"title":"Switching From Active Vitamin d and Phosphate Supplementation to Burosumab Significantly Corrects Lower Limb Malalignment in Pediatric X-Linked Hypophosphatemia.","authors":"Leanne M Ward, Erik A Imel, David Frumberg, Lisa Dilworth, Catherine Siener, Zunqiu Chen, Stanley Krolczyk, Thomas O Carpenter","doi":"10.1093/jbmr/zjaf079","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf079","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a rare disorder of renal phosphate wasting and dysregulated active vitamin D metabolism, ultimately presenting as rickets and osteomalacia, among other manifestations. Lower extremity deformity (genu valgum and/or varum) is frequent in this pediatric population. Despite prompt active vitamin D and phosphate supplementation (active D/Pi), many patients require corrective surgery for lower limb malformation. Burosumab has demonstrated improvements in lower limb malalignment in children with XLH in several studies. We expand on those reports by assessing mechanical femoral tibial angle (mFTA) change in patients enrolled in the XLH Disease Monitoring Program (DMP), (NCT03651505) to determine the impact of initiating burosumab treatment after a history of active D/Pi. Included patients had either switched from active D/Pi to burosumab treatment at the discretion of their treating physician or as part of a burosumab clinical trial, or remained on active D/Pi through Year 3 of the DMP. Year 3 radiographs were compared with baseline to assess mFTA change and gauge improvement. Additional multivariate factor analysis examined 24 attributes to determine which had the greatest association with mFTA change. Change in mFTA was assessed for each limb independently. A greater proportion of limbs of patients switching from active D/Pi to burosumab had improved mFTA compared with those remaining on active D/Pi (p < .023). Odds ratios comparing limbs that improved to those that did not showed that switching to burosumab yields a significantly greater chance of improvement than continuing active D/Pi (OR [95% CI]: 4.38 [1.09-17.50]; p = .0469). Factor analysis identified younger age at burosumab initiation (p = .001) and lower baseline height Z-score (p = .006) as being significantly associated with greater change in mFTA Z-score. This study shows that switching to burosumab significantly improves lower limb malalignment in children with XLH over benefits conferred by active D/Pi, with early burosumab initiation providing the greatest benefit.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281824","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}

{"title":"Time-lapse HR-pQCT reliably assesses and monitors local bone turnover in patients with chronic kidney disease.","authors":"Minhao Zhou, Saghi Sadoughi, Lauren Go, Gabriella Ramil, Isabel Yu, Isra Saeed, Bo Fan, Po-Hung Wu, Isidro B Salusky, Thomas L Nickolas, Joachim H Ix, Galateia J Kazakia","doi":"10.1093/jbmr/zjaf006","DOIUrl":"10.1093/jbmr/zjaf006","url":null,"abstract":"<p><p>Bone turnover assessment and monitoring are essential for chronic kidney disease (CKD)-associated bone care. Patients with CKD suffer from significantly elevated fracture risk due to abnormally high or low bone turnover, which benefits from diametrically opposite treatments informed by patient-specific bone turnover data. However, a reliable, accessible, noninvasive bone turnover assessment and monitoring tool remains an unmet clinical need. Combining time-lapse (TL) analysis with high-resolution peripheral quantitative computed tomography (HR-pQCT) scans obtained over time allows for in vivo temporospatial bone remodeling assessment. This study aimed to evaluate the feasibility of applying TL HR-pQCT to assess and monitor local bone formation and resorption in patients with CKD. A customized TL HR-pQCT pipeline was developed on a second-generation HR-pQCT platform and optimized using both ex vivo cadaveric phantom and in vivo scan-rescan HR-pQCT images. The annualized least significant changes in bone formation and resorption were evaluated using in vivo longitudinal reproducibility images. Finally, the feasibility of the TL HR-pQCT pipeline in assessing and monitoring bone turnover was evaluated in patients with end-stage kidney disease (ESKD; n = 9). We found that a 2-month TL period was sufficient for the TL HR-pQCT pipeline to reliably assess and monitor local bone turnover in a cohort of patients with ESKD. We also demonstrated the importance of characterizing TL HR-pQCT precision metrics using longitudinal baseline/follow-up rather than short-term scan-rescan datasets. The TL HR-pQCT pipeline assessed a range of bone formation metrics agreeing with the gold-standard histomorphometry bone formation reported in the literature for patients with CKD and ESKD. Our findings highlight that TL HR-pQCT holds promise as a \"virtual bone biopsy\" that reliably assesses and monitors local bone turnover for CKD bone care. Subsequent work will focus on validating this TL HR-pQCT pipeline against the gold-standard bone biopsy with quantitative histomorphometry.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"738-752"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982050","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}

{"title":"Probability of achieving bone mineral density treatment goals with denosumab treatment in postmenopausal women with osteoporosis.","authors":"Felicia Cosman, Zhenxun Wang, Xiaodong Li, Steven R Cummings","doi":"10.1093/jbmr/zjaf014","DOIUrl":"10.1093/jbmr/zjaf014","url":null,"abstract":"<p><p>BMD levels achieved on osteoporosis treatment are predictive of subsequent fracture risk, and T-score >-2.5 has been proposed as a minimum treatment target for women with osteoporosis. Knowing the likelihood of attaining target T-scores with different medications for different baseline BMD levels can help determine appropriate initial treatment for individual patients. In this post hoc analysis, we estimated the probability of achieving a non-osteoporotic T-score (>-2.5 or ≥-2.0) at the TH or LS in postmenopausal women >60 yr old treated with denosumab for either 3 or 10 yr in the FREEDOM trial and its long-term extension. In women with baseline TH T-scores of -2.7, -3.0, and -3.5, the probabilities of achieving target T-scores >-2.5 with 3 yr of denosumab were 71%, 12%, and 0.1%, respectively. At LS, for baseline T-scores of -2.7, -3.0, and -3.5, the probabilities were 86%, 59%, and 11%, respectively. Longer treatment duration of up to 10 yr increased the probability of achieving target T-scores. The baseline T-scores that permitted at least 50% of women to achieve a target T-score >-2.5 were -2.8 at TH and -3.1 at LS after 3 yr and -3.0 at TH and -3.7 at LS after 10 yr of treatment. To achieve higher treatment targets (T-scores ≥ -2.0), overall probabilities were lower at both skeletal sites, particularly for TH, even with longer treatment duration. Our results demonstrate that the probability of achieving T-score targets with denosumab is dependent on baseline BMD, skeletal site, and treatment duration. Knowing the probability of achieving treatment targets for different baseline TH and LS T-scores can help determine whether denosumab is an appropriate first choice of treatment in individual patients.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"766-772"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of calcium supplementation on bone calcium balance and calcium and bone metabolism during load carriage in women: a randomized controlled crossover trial.","authors":"Charlotte V Coombs, Julie P Greeves, Christina D Young, Alice S Irving, Anton Eisenhauer, Ana Kolevica, Alexander Heuser, Jonathan C Y Tang, William D Fraser, Thomas J O'Leary","doi":"10.1093/jbmr/zjaf004","DOIUrl":"10.1093/jbmr/zjaf004","url":null,"abstract":"<p><p>Calcium supplementation before exercise attenuates the decrease in serum calcium and increase in PTH and bone resorption. This study investigated the effect of calcium supplementation on calcium and bone metabolism during load carriage in women. A total of 48 women completed two load carriage sessions (load carriage 1 n = 48; load carriage 2 n = 40) (12.8 km in 120 min carrying 20 kg) 60 min after consuming either 1000 mg calcium (Calcium) or nothing (Control) in a randomized order. Pre- and post-exercise urine samples were analyzed for calcium isotope ratio (δ44/42Ca). Fasted blood samples were taken before (pre-exercise), during (0, 20, 40, 60, 80, 100, 120 min), and after (+15, +30, +60, +90 min) exercise and analyzed for markers of calcium and bone metabolism. There was no effect of load carriage or supplementation on urine δ44/42Ca (p ≥ .110). Serum δ44/42Ca did not change with load carriage in Control (p = .617) but increased in Calcium (p = .003) and was higher at 120 min in Calcium vs Control (p = .018). Ionized calcium (iCa) decreased from pre-exercise to all exercise time-points (p < .001); iCa was higher in Calcium than Control throughout (p < .001). PTH increased from pre-exercise to 120 min in Control (p < .001) but decreased from pre-exercise to all time-points in Calcium (p < .001). PTH was higher in Control than Calcium from 0 to +90 min (p < .001). βCTX decreased from pre-exercise to 20 to +15 min in Control (p ≤ .004); βCTX decreased from pre-exercise to 0 to +90 min in Calcium (p < .001). βCTX was lower in Calcium than Control from 20 to +90 min (p ≤ .036). A 1000 mg calcium supplement before load carriage promotes bone calcium balance and prevents disruptions to bone and calcium homeostasis. Clinical trial registration: NCT04823156 (ClinicalTrials.gov).</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"753-765"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969024","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}

{"title":"Prediction of hip fracture by high-resolution peripheral quantitative computed tomography in older Swedish women.","authors":"Raju Jaiswal, Aldina Pivodic, Michail Zoulakis, Kristian F Axelsson, Henrik Litsne, Lisa Johansson, Mattias Lorentzon","doi":"10.1093/jbmr/zjaf020","DOIUrl":"10.1093/jbmr/zjaf020","url":null,"abstract":"<p><p>The socioeconomic burden of hip fractures, the most severe osteoporotic fracture outcome, is increasing and the current clinical risk assessment lacks sensitivity. This study aimed to develop a method for improved prediction of hip fracture by incorporating measurements of bone microstructure and composition derived from HR-pQCT. In a prospective cohort study of 3028 community-dwelling women aged 75-80, all participants answered questionnaires and underwent baseline examinations of anthropometrics and bone by DXA and HR-pQCT. Medical records, a regional x-ray archive, and registers were used to identify incident fractures and death. Prediction models for hip, major osteoporotic fracture (MOF), and any fracture were developed using Cox proportional hazards regression and machine learning algorithms (neural network, random forest, ensemble, and Extreme Gradient Boosting). In the 2856 (94.3%) women with complete HR-pQCT data at 2 tibia sites (distal and ultra-distal), the median follow-up period was 8.0 yr, and 217 hip, 746 MOF, and 1008 any type of incident fracture occurred. In Cox regression models adjusted for age, BMI, clinical risk factors (CRFs), and FN BMD, the strongest predictors of hip fracture were tibia total volumetric BMD and cortical thickness. The performance of the Cox regression-based prediction models for hip fracture was significantly improved by HR-pQCT (time-dependent AUC; area under receiver operating characteristic curve at 5 yr of follow-up 0.75 [0.64-0.85]), compared to a reference model including CRFs and FN BMD (AUC = 0.71 [0.58-0.81], p < .001) and a Fracture Risk Assessment Tool risk score model (AUC = 0.70 [0.60-0.80], p < .001). The Cox regression model for hip fracture had a significantly higher accuracy than the neural network-based model, the best-performing machine learning algorithm, at clinically relevant sensitivity levels. We conclude that the addition of HR-pQCT parameters improves the prediction of hip fractures in a cohort of older Swedish women.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"779-790"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell RNA sequencing shows that cells expressing Sox9 postnatally populate most skeletal lineages in mouse bone.","authors":"Neal P Smith, Christopher Janton, Ana Clara Morellato Alcantara, Majd George, Kasidet Mankongtreecheep, Guping Mao, Alexandra-Chloé Villani, Henry M Kronenberg","doi":"10.1093/jbmr/zjaf043","DOIUrl":"10.1093/jbmr/zjaf043","url":null,"abstract":"<p><p>In growing bones of mice, multiple cell types contribute to the osteoblast lineage, including growth plate chondrocytes, perichondrial cells and CXCL12-abundant reticular marrow stromal cells. Here we use single-cell RNA sequencing and lineage tracing to show that all these osteoblast precursors, even postnatally, derives from Sox9-expressing progenitors. We also characterize a distinct group of chondrocytes located between the perichondrium and the columns of growth plate chondrocytes that contribute to the osteoblast lineage.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"799-812"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717814","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}

{"title":"Structural alterations during fracture healing lead to void spaces developing in surrounding bone microarchitecture.","authors":"Danielle E Whittier, Matthias Walle, Penny R Atkins, Caitlyn J Collins, Matthias A Zumstein, Patrik Christen, Kurt Lippuner, Ralph Müller","doi":"10.1093/jbmr/zjaf046","DOIUrl":"10.1093/jbmr/zjaf046","url":null,"abstract":"<p><p>Distal radius fractures are among the most common fracture sites, with a high incidence across all age groups. High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled assessment of bone microarchitecture in vivo at the distal radius, providing new insights into the healing process. However, we have observed structural bone loss that is not captured by standard analysis. This study uses void space analysis to quantify the development of localized structural bone loss during fracture healing. Twenty-six participants (21 female, 5 male; aged 18-79 yr) with conservatively-treated distal radius fractures were scanned using HR-pQCT at 6 study visits post-fracture (wk 1, 3, 5, 12, 26, and 52). Total BMD (Tt.BMD), bone volume fraction (BV/TV), and void space volume fraction (VS/TV) were measured. Grip strength relative to the non-fractured wrist and patient rated wrist evaluation (PRWE) were measured at all study visits after cast removal. The cumulative expansion of VS/TV across sequential study visits was quantified to differentiate voids that developed during healing from pre-existing void space. A 5-fold increase in median VS/TV was observed during the follow-up period, from 1.0% (0.6%-9.0%) to 5.5% (2.5%-12.4%). Tt.BMD and BV/TV did not significantly change in this same time interval. Relative grip strength after cast removal was significantly inversely correlated with final VS/TV (⍴ = -0.63, p = .02) and cumulative expansion of new void space during healing (R = -0.67, p <.01), whereas no significant associations were found with age or PRWE. This study suggests that there are adverse changes in bone microarchitecture during fracture healing, despite the preservation of overall Tt.BMD and BV/TV in the same region. Reduced grip strength is correlated with more severe void space formation, but the mechanistic relationship requires further exploration. The formation of void spaces may have long-term implications on bone strength and could provide insight into risk of re-fracture.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"791-798"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages regulate angiogenesis-osteogenesis coupling induced by mechanical loading through the Piezo1 pathway.","authors":"Hongzhi Liu, Hang Zhou, Yuanhao Fan, Jiawei Li, Ziyu Guo, Qiuchi Xu, Yang Liu, Kun Gao, Neima Ait Lahcine, Jianing Zhang, Jingjing Zhou, Fengjin Guo, Chao Liu","doi":"10.1093/jbmr/zjae198","DOIUrl":"10.1093/jbmr/zjae198","url":null,"abstract":"<p><p>Bone is a mechanosensitive organ, and its regeneration also depends on the ability of bone cells to perceive and react to mechanical stimuli. Macrophages are indispensable for bone formation, regeneration, and maintenance. Depletion of macrophages resulted in poor bone development due to impaired vessel formation and osteogenesis. However, how mechanical stimulation stimulates macrophages during bone regeneration is unclear. As in many cell types, Piezo1 is part of the mechanotransduction in macrophages and modulates macrophage activity. Here, we utilized conditional KO of Piezo1 in LysM+ myeloid cells and in vivo mechanical loading to investigate the mechanoregulation of macrophages and their contribution to bone repair. We found that mechanical loading increased the ratio of CD206+ macrophages, angiogenesis-osteogenesis coupling, and cell proliferation within the defect region, leading to enhanced bone regeneration. However, all the loading-induced upregulations were blunted by the conditional KO of Piezo1 in macrophages. Furthermore, we implanted WT bone marrow-derived macrophages into the defect area in Piezo1 KO mice. WT macrophages rescued mechanosensitive angiogenesis-osteogenesis coupling and promoted bone regeneration in Piezo1 KO mice. Together, our data showed that Piezo1 in macrophages is indispensable for loading-induced bone regeneration by stimulating macrophage polarization into the CD206+ phenotype, thereby facilitating the angiogenesis-osteogenesis coupling, promoting cell proliferation, and finally resulting in enhanced bone regeneration.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"725-737"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826574","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}