Journal of Orthopaedic Translation最新文献

{"title":"Silence of HOTAIR promotes osteogenic differentiation and accelerates distraction osteogenesis by mediating FTO ubiquitination","authors":"Xiao-min Wu ,&nbsp;Yong-xin Mai ,&nbsp;Yong-fa Wen ,&nbsp;Zhi-peng Li ,&nbsp;Yu-xin Sun ,&nbsp;Jun-jing Chen ,&nbsp;Fengzhen Meng ,&nbsp;feng-xiang Pang ,&nbsp;Huai-ming Li ,&nbsp;Yu Pan ,&nbsp;Jin-fang Zhang ,&nbsp;Xiao-hua Pan","doi":"10.1016/j.jot.2024.12.001","DOIUrl":"10.1016/j.jot.2024.12.001","url":null,"abstract":"<div><h3>Background</h3><div>Distraction osteogenesis(DO) is a valuable bone regeneration technique, yet its prolonged consolidation phase often entails pain, high costs, infection risks, and lifestyle disruptions. Finding adjunctive approaches to shorten treatment duration is thus of clinical significance. Long noncoding RNAs have been demonstrated to play pivotal roles in regulating bone formation, and homeobox transcript antisense intergenic RNA(HOTAIR) was also reported to regulate osteogenesis and bone formation. However, its role in DO remains unclear.</div></div><div><h3>Methods</h3><div>The effects of HOTAIR on osteogenesis were examined in rat bone marrow-derived mesenchymal stem cells(BMSCs) by asssessing ALP activity, calcification, and osteogenic gene expression with HOTAIR knockdown or overexpression. Using a tibial DO model, HOTAIR-stably silenced BMSCs or control cells were locally injected into the percutaneous distraction gap, and the effects were evaluated by micro-CT, dual-energy X-ray examination, mechanical testing, hematoxylin and eosin staining, and immunohistochemistry.</div></div><div><h3>Results</h3><div>In the present study, it was found that HOTAIR silence promoted while its overexpression suppressed the osteogenic differentiation of BMSCs<em>.</em> The Mechanistic study revealed that HOTAIR physically interacted with FTO, and disrupted FTO ubiquitination and degradation, leading to FTO up-regulation and suppressing osteogenesis. Using DO animal model, HOTAIR-silenced BMSCs stimulated new bone formation and accelerated DO healing <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>Silence of HOTAIR enhanced osteogenesis in BMSCs and facilitated DO healing by recruiting FTO and inducing its degradation.</div></div><div><h3>Translational potential</h3><div>The findings generated from this study suggest that inhibitor of HOTAIR may be developed as a promising strategy for DO patients.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 248-256"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080450","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":"Cracking the code: Understanding ESWT's role in bone fracture healing","authors":"Nan Jing ,&nbsp;Yi-chen Hou ,&nbsp;Jia-chang Zhang ,&nbsp;Guangyu Xu ,&nbsp;Mingcheng Lei ,&nbsp;Xiaobin Tang ,&nbsp;Wei Chen ,&nbsp;Hongbin Ni ,&nbsp;Feng Zhang","doi":"10.1016/j.jot.2024.11.006","DOIUrl":"10.1016/j.jot.2024.11.006","url":null,"abstract":"<div><div>Bone non-union has always been a research hotspot in the field of orthopedics. Non-unions are often accompanied by symptoms such as pain, deformity, and dysfunction, which can significantly affect patients’ quality of life and cause related socioeconomic problems. Clinically, there are various treatments available for non-unions, and the main treatment methods are divided into surgical and non-surgical treatments. At present, surgery is the most widely used treatment for bone non-unions and has a high healing rate. However, even after surgery, some patients still face the problem of bone non-union. Furthermore, a small number of patients have surgical contraindications and could not tolerate surgery. Therefore, alternative treatments are needed to improve outcomes for patients with bone fractures. Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment method with similar efficacy and better safety compared with surgery. Nevertheless, the exact mechanism for ESWT to treat patients with bone non-union are still not well understood. This article reviews the mechanisms of ESWT in promoting bone fracture healing by regulating osteoblasts and osteoclasts, providing a theoretical foundation for the clinical application of ESWT.</div><div>The Translational Potential of this Article: This review provides a comprehensive overview of the mechanisms underlying ESWT on promoting bone fracture healing by regulating osteoblasts and osteoclasts. The information provided in this article can offer a novel non-invasive method for clinicians to treat bone non-union.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 403-412"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600500","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":"Repair of the femoral head osteochondral defect in a swine model using autologous costal cartilage graft transplantation","authors":"Fuchou Hsiang ,&nbsp;Yun Gao ,&nbsp;Yiyang Ma ,&nbsp;Peichun Hsu ,&nbsp;Cheng Qiu ,&nbsp;Kaiwen Zheng ,&nbsp;Yidan Pang ,&nbsp;Jinyu Zhu ,&nbsp;Weibin Yu ,&nbsp;Chun Chen ,&nbsp;Changqing Zhang ,&nbsp;Dajiang Du","doi":"10.1016/j.jot.2024.10.007","DOIUrl":"10.1016/j.jot.2024.10.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Mosaic transplantation using autologous osteochondral graft (AOCG) is an effective treatment for osteochondral lesion however, at the sacrifice of irreversible damage to the donor articular surface. Costal cartilage is hyaline cartilage and has been utilized as a donor source in various surgeries. This study investigates the use of autologous costal cartilage graft (ACCG) for treating femoral head osteochondral defects in a swine model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Osteochondral defects were surgically induced in the femoral heads of one-year-old Bama pigs regardless of sex. The swine were divided into a Defect group without grafting (n = 6), a group grafted with ACCG (n = 6) and a group grafted with AOCG from ipsilateral trochlear groove (n = 6). Postoperatively, swine were allowed free cage activity without immobilization and were euthanized at either 3 or 6 months. Repair effects were evaluated using μCT, MRI, histology and immunohistochemistry (IHC) to assess the osteochondral properties of the grafted femoral head.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;There was no difference in the hip function of the Bama pigs between AOCG and ACCG groups. The International Cartilage Repair Society (ICRS) scores showed no difference between AOCG and ACCG at both time points. ACCG exhibited comparable trabecular thickness as AOCG's, but lower trabecular number and higher trabecular separation. Percent bone volume was significantly lower in the ACCG group when compared to AOCG at 3 months, but not at 6 months. Modified MOCART scores were significantly higher in the AOCG group at 3 months but not at 6 months. MRI also detected increasing degree of ossification in the costal cartilage graft at all time points. Histologically, ACCG formed a subchondral bone interface while maintaining the hyaline cartilage characteristics on the articular surface. We also found that superficial layer of ACCG integrated more thoroughly with the recipient cartilage than AOCG did. Furthermore, histology and IHC collectively demonstrated that ACCG had undergone endochondral ossification process at the subchondral layer, evidenced by increased type I collagen expression and decreased type II collagen expression. No donor-site morbidity was noted with ACCG procedure during the study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study demonstrates that ACCG can serve as a viable alternative to AOCG for treating femoral head osteochondral defects. The findings show that ACCG offers comparable outcomes to AOCG while avoiding the donor-site morbidity associated with AOCG. Given the challenges related to the donor tissue availability and associated complications in the clinical practice, ACCG could provide a promising and less invasive option for cartilage repair.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;This proposed method can be translated into practical treatment for repairing osteochondral lesion in human hip joints","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 413-422"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600499","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":"Unveiling MiR-3085-3p as a modulator of cartilage degeneration in facet joint osteoarthritis: A novel therapeutic target","authors":"Zhong-ming Lai ,&nbsp;Cheng-long Li ,&nbsp;Jun-xiong Zhang,&nbsp;Xiang Ao,&nbsp;Cheng-shuo Fei,&nbsp;Xin Xiang,&nbsp;Yan-lin Chen,&nbsp;Ze-sen Chen,&nbsp;Rui-qian Tan,&nbsp;Liang Wang,&nbsp;Zhong-min Zhang","doi":"10.1016/j.jot.2024.11.007","DOIUrl":"10.1016/j.jot.2024.11.007","url":null,"abstract":"<div><h3>Background</h3><div>Low back pain (LBP) is generally caused by lumbar degeneration without effective treatment. Lumbar degeneration is influenced by aberrant axial mechanical stress (MS), with facet joint osteoarthritis (FJOA) representing one of its primary pathological manifestations. MicroRNA (miRNA), functioning as an early intermediate in the transcription process, has frequently been demonstrated to serve as a critical mediator linking mechanical stress perception with cellular processes such as growth, development, aging, and apoptosis. We hypothesized that miR-3085-3p regulates chondrocyte apoptosis under mechanical stress, influencing FJOA and serving as a key regulator.</div></div><div><h3>Methods</h3><div>The severity of cartilage degeneration in bipedal standing models (BSM) was established and validated through micro-CT and histopathology. Cyclic tensile strain experiments (CTS) were conducted on the ATDC5 cell line to simulate MS. In situ hybridization was utilized to assess the expression levels of miR-3085-3p in degraded facet articular cartilage. The role of miR-3085-3p and its interaction with the downstream mRNA target Hspb6 were investigated through a combination of bioinformatic analysis, quantitative real-time polymerase chain reaction, western blotting, immunofluorescence, and luciferase assay. In vivo experiments on BSM, the functional impact of miR-3085-3p was further examined through transfection with adeno-associated virus (AAV).</div></div><div><h3>Results</h3><div>It was observed that miR-3085-3p induced endoplasmic reticulum (ER) stress and apoptosis in chondrocytes and cartilage tissues under MS. The detrimental impact of miR-3085-3p was associated with the downregulation of Hspb6 expression, resulting in disruption of endoplasmic reticulum folding function. Additionally, intra-articular transfection of AAV miR-3085-3p mimics in mice facet joints led to spontaneous cartilage loss, while AAV miRNA-3085-3p sponge administration mitigated FJOA in the murine BSM model.</div></div><div><h3>Conclusion</h3><div>Mechanical stress-regulated miR-3085-3p up regulation induced the ER stress and aggravates FJOA development through targeting HSPB6, suggesting miR-3085-3p may be a novel therapeutic target for FJOA.</div><div>Translational potential of this article: Our study confirmed the elevated expression of miR-3085-3p in lumbar facet joints following mechanical stress loading, suggesting that miR-3085-3p may serve as a biomarker for the clinical management of FJOA. Additionally, we demonstrated that the knockdown of miR-3085-3p in animal facet joints mitigated facet joint degeneration, thereby identifying a potential therapeutic target for FJOA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 235-247"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079368","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":"Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study","authors":"Daxue Zhu ,&nbsp;Zhaoheng Wang ,&nbsp;Yanhu Li ,&nbsp;Shijie Chen ,&nbsp;Xuewen Kang","doi":"10.1016/j.jot.2024.12.002","DOIUrl":"10.1016/j.jot.2024.12.002","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IDD) is a prevalent etiology of low back pain in the global adult population, leading to considerable morbidity and healthcare costs. Existing therapeutic modalities for IDD remain constrained. Ferroptosis in the nucleus pulposus (NP) cells emerges as a pivotal contributor to IDD. Humanin (HN), a mitochondrial-secreted peptide, is intricately linked to age-related maladies and showcases antioxidant, anti-inflammatory, and anti-apoptotic properties. Nonetheless, its precise involvement in IDD remains enigmatic.</div></div><div><h3>Methods</h3><div>The expression profile of HN in IDD was scrutinized utilizing human NP cell cultures and an IDD rat model (n = 5). The therapeutic efficacy of HN in rats was assessed via MRI and histological evaluation, alongside an exploration of the molecular underpinnings of HN's therapeutic actions in IDD management.</div></div><div><h3>Results</h3><div>This pioneering study unveiled a downregulation of HN expression in IDD patients, a finding corroborated through cell and rat IDD models. Furthermore, it was ascertained that exogenous HN could trigger endogenous HN expression, impede the JAK2/STAT3 and NF-κB pathways, thereby mitigating erastin-induced ferroptosis in NP cells, contingent upon the upregulation of HSP27 expression. Moreover, the study validated the role of HN in preserving mitochondrial homeostasis, curbing mitochondrial reactive oxygen species (mtROS) generation and mtDNA leakage, consequently hindering mtDNA binding to TLR9 and subsequent activation of the NF-κB pathway. Notably, in vivo rat experiments underscored the efficacy of HN treatment in ameliorating IDD progression induced by annulus fibrosus puncture.</div></div><div><h3>Conclusion</h3><div>By assuaging ferroptosis in NP cells, HN exhibits promise as a viable candidate for IDD treatment, capable of impeding disease advancement. <strong>The translational potential of this article</strong>: This study highlights the importance and effectiveness of HN in alleviating IDD by inhibiting ferroptosis in NP cells. The addition of exogenous HN may represent a potential therapeutic strategy for treating IDD.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 274-294"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122909","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":"Application of collagen in bone regeneration","authors":"Rou Li ,&nbsp;Shiqing Xu ,&nbsp;Yanning Guo ,&nbsp;Cong Cao ,&nbsp;Jingchen Xu ,&nbsp;Lijun Hao ,&nbsp;Sai Luo ,&nbsp;Xinyao Chen ,&nbsp;Yuyang Du ,&nbsp;Ye Li ,&nbsp;Yong Xie ,&nbsp;Weitong Gao ,&nbsp;Jing Li ,&nbsp;Baohua Xu","doi":"10.1016/j.jot.2024.10.002","DOIUrl":"10.1016/j.jot.2024.10.002","url":null,"abstract":"<div><div>At present, there is a significant population of individuals experiencing bone deficiencies caused by injuries, ailments affecting the bones, congenital abnormalities, and cancer. The management of substantial bone defects a significant global orthopedic challenge due to the intricacies involved in promoting and restoring the growth of fresh osseous tissue. Autografts are widely regarded as the “gold standard” for repairing bone defects because of their superior tissue acceptance and ability to control osteogenesis. However, patients undergoing autografts may encounter various challenges, including but not limited to hernia, bleeding, nerve impairment, tissue death. Therefore, researchers in regenerative medicine are striving to find alternatives. Collagen is the most abundant protein in the human body, and its triple helix structure gives it unique characteristics that contribute to its strength and functionality in various tissues. Collagen is commonly processed into various forms such as scaffolds, sponges, membranes, hydrogels, and composite materials, due to its unique compatibility with the human body, affinity for water, minimal potential for immune reactions, adaptability, and ability to transport nutrients or drugs. As an alternative material in the field of bone regeneration, collagen is becoming increasingly important. The objective of this review is to provide a comprehensive analysis of the primary types and sources of collagen, their processes of synthesis and degradation, as well as the advancements made in bone regeneration research and its potential applications. A comprehensive investigation into the role of collagen in bone regeneration is undertaken, providing valuable points of reference for a more profound comprehension of collagen applications in this field. The concluding section provides a comprehensive overview of the prospective avenues for collagen research, underscoring their promising future and highlighting their significant potential in the field of bone regeneration.</div><div>The Translational Potential of this Article. The comprehensive exploration into the diverse functions and translational potential of collagen in bone regeneration, as demonstrated in this review, these findings underscore their promising potential as a treatment option with significant clinical implications, thus paving the way for innovative and efficacious therapeutic strategies in this domain.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 129-143"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177809","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":"Charting a quarter-century of commercial cartilage regeneration products","authors":"Xinyi Liu ,&nbsp;Xiaolei Guo ,&nbsp;Yixuan Amy Pei ,&nbsp;Ming Pei ,&nbsp;Zigang Ge","doi":"10.1016/j.jot.2024.10.009","DOIUrl":"10.1016/j.jot.2024.10.009","url":null,"abstract":"<div><div>Functional cartilage regeneration remains difficult to achieve despite decades of research. Dozens of commercial products have been proposed, with each targeting different facets of successful cartilage engineering, including mechanical properties, integration, lubrication and inflammation; however, there remains a lack of breakthroughs in meaningful clinical outcomes. Prior research categorized commercial products based on their components and elucidated challenges faced during the market approval process. This paper, for the first time, comprehensively reviews the properties of commercial products covering the last 25 years, including design trends in components, compatibility with minimally invasive surgery, indications for cartilage defects, long-term follow-up, as well as active sponsorship support of the International Cartilage Regeneration and Joint Preservation Society (ICRS). We aim to summarize the key factors for potentially successful commercial products and elucidate overarching trends in technology development in this field. Given that no revolutionary products have yielded significantly improved clinical results, emerging products compete with one another on user-friendliness and cost-efficiency. Other relevant characteristics include compatibility with minimally invasive surgery, extensiveness of required surgery (one-stage vs. two-stage), use of versatile artificial polymers and application of cells and biomaterials. Specific products continue to lead the market due to their cost-efficiency or indications for larger cartilage defects. However, they have been shown to result in no significant improvement upon clinical follow-up. Thus, there is a need for products that surpass current commercial products and show clinical effectiveness.</div><div><strong>Translation potential of this article</strong>: This review analyzes product components, compatibility with minimally invasive surgery, indication for cartilage defect areas, clinical performance as well as sponsorship for the World Conference of International Cartilage Regeneration &amp; Joint Preservation Society, based on information about cartilage regeneration products from 1997 to 2023. It shines a light on future development of design and commercialization of cartilage products.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 354-363"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177861","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":"Moldable self-setting and bioactive bone wax for bone hemostasis and defect repair","authors":"Ziyang Liu ,&nbsp;Chuang Liu ,&nbsp;Huan Zhou ,&nbsp;Chunyong Liang ,&nbsp;Wei Chen ,&nbsp;Yanjie Bai ,&nbsp;Xinlong Ma ,&nbsp;Yingze Zhang ,&nbsp;Lei Yang","doi":"10.1016/j.jot.2024.11.009","DOIUrl":"10.1016/j.jot.2024.11.009","url":null,"abstract":"<div><h3>Objective</h3><div>Bone injury complicated with bleeding and irregular shaped defect are challenging in orthopedic surgery and practices due to the lack of reliable hemostasis and simultaneous defect repair strategy. Bone wax is a century-old biomaterial for bleeding management in orthopedic surgery, characterized with ready-to-use advantage but the risk of failed bone reunion due to the biological inertness and non-degradability. In current work, integration of bioceramic cement and premixed concept was motivated to prepare a in situ self-setting bioactive calcium phosphate based bone wax (CaPBW) for bone hemostasis and defect repair.</div></div><div><h3>Methods</h3><div>A moldable, in situ self-setting bioactive CaPBW with a novel formulation of calcium phosphate cement (CPC), monetite (DPCA) granules, modified starch and polyethylene glycol (PEG) was developed for bone hemostasis and defect repair. The CaPBW material was evaluated by characterization, physical and chemical properties, biocompatibility, osteogenic ability and hemostatic ability.</div></div><div><h3>Results</h3><div>CaPBW adopted the ready-to-use feature of traditional bone wax, showing feasibility in shape molding and defect sealing. When interacted with physiological fluid like blood, CaPBW could transformed from putty to solid state within tens of minutes due to the gradual PEG-water exchange and CPC hydration, providing mechanical stability for bleeding clotting and bone defect filling. <em>In vitro</em> studies revealed the superiority of CaPBW over bone wax in blood coagulation and osteoblast differentiation, along with hemocompatibility and osteogenesis confirmation. <em>In vivo</em> studies demonstrated the reliability of CaPBW in hemostasis and bone regeneration compared to traditional bone wax, promoting the efficacy of bone bleeding and new bone formation.</div></div><div><h3>Conclusion</h3><div>As compared to traditional bone hemostatic agent bone wax, CaPBW not only preserved its advantages in handling and defect sealing, but also provided platform for temporary physical support and bone regeneration acceleration.</div></div><div><h3>The translational potential of this article</h3><div>The integrated design of osteogenesis and hemostasis makes CaPBW have the dual functions as bone hemostasis material and artificial bone substitute. CaPBW therefore demonstrates a strategy of next-generation bone wax with high translational potential for orthopedic surgery.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 223-234"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080384","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":"A novel application perspective of the clinical-used drug verapamil on osteoporosis via targeting Txnip","authors":"Xiankun Cao ,&nbsp;Kewei Rong ,&nbsp;Yinghua Li ,&nbsp;Pu Zhang ,&nbsp;Kexin Liu ,&nbsp;Lei Cui ,&nbsp;Shaotian Fu ,&nbsp;Qi Hua ,&nbsp;Xiao Yang ,&nbsp;Hang Zhang ,&nbsp;Xiaofei Cheng ,&nbsp;Peixiang Ma ,&nbsp;Jie Zhao ,&nbsp;An Qin","doi":"10.1016/j.jot.2024.10.006","DOIUrl":"10.1016/j.jot.2024.10.006","url":null,"abstract":"<div><h3>Background</h3><div>RANKL and SCLEROSTIN antibodies have provided a strong effective choice for treating osteoporosis in the past years, which suggested novel molecular target identification and therapeutic strategies development are important for the treatment of osteoporosis. The therapeutic effect of verapamil, a drug previously used for cardiovascular diseases, on diabetes was due to the inhibition of TXNIP expression, which has also been reported as a target in mice osteoporosis. Whether verapamil-inhibited TXNIP expression is related to osteoporosis and how it works on the molecular level is worthy to be explored.</div></div><div><h3>Methods</h3><div>The polymorphism genotyping analysis was performed on patients with different degrees of osteoporosis. The responsiveness of bone marrow-derived macrophage cells (bone marrow-derived mesenchymal stem cells) to verapamil was evaluated by CCK-8, TRAP staining assay (ALP and AR staining assay), Bone Resorption Assay, and RNA-Sequencing. The expression and cytoplasmic efflux of ChREBP were determined by western blotting and immunofluorescence. Bilateral ovariectomy models were created, rescued by verapamil injection and the effectiveness was evaluated by Micro-CT and Histological analysis.</div></div><div><h3>Results</h3><div>Here we discovered that rs7211 single nucleotide polymorphism (SNP) of <em>TXNIP</em> is closely associated with increased femur neck bone mineral density (BMD) and decreased osteoporosis rate, suggesting the importance of TXNIP in the development of osteoporosis. Verapamil suppresses <em>Txnip</em> expression, reduces bone turnover rate and thus rescues ovariectomy-induced mice bone loss. Mechanistically, verapamil promoted ChREBP cytoplasmic efflux, regulated Pparγ expression both mediating Txnip-MAPK, NF-<span><math><mrow><mi>κ</mi></mrow></math></span> B axis in osteoclasts, and suppressed the ChREBP-Txnip-Bmp2 axis in osteoblasts.</div></div><div><h3>Conclusions</h3><div>The results of our study show the correlation of rs7211 <em>TXNIP-T</em> allele with Chinese increased femur neck BMD and decreased osteoporosis rate. In addition, verapamil can rescue mice from osteoporosis by regulateing ChREBP, Pparγ-Txnip-MAPK, NF-<span><math><mrow><mi>κ</mi></mrow></math></span> B axis in osteoclasts and ChREBP-Txnip-Bmp2 axis in osteoblasts.</div></div><div><h3>The translational potential of this article</h3><div>The inhibition of Txnip by verapamil in osteoclasts and osteoblasts leads to low bone turnover and reduced bilateral ovariectomy-induced mice bone loss, which points out its great clinical translation potential on postmenopausal osteoporosis treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 158-173"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059330","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":"Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles","authors":"Shanfeng Chen ,&nbsp;Yiming Dou ,&nbsp;Yiming Zhang ,&nbsp;Xun Sun ,&nbsp;Xinyu Liu ,&nbsp;Qiang Yang","doi":"10.1016/j.jot.2024.09.014","DOIUrl":"10.1016/j.jot.2024.09.014","url":null,"abstract":"<div><div>Intervertebral disc degeneration is the leading cause of low back pain, imposing significant burdens on patients, societies, and economies. Advancements in regenerative medicine have spotlighted extracellular vesicles as promising nanoparticles for intervertebral disc degeneration treatment. Extracellular vesicles retain the potential of cell therapy and serve as carriers to deliver their cargo to target cells, thereby regulating cell activity. This review summarizes the biogenesis and molecular composition of extracellular vesicles and explores their therapeutic roles in intervertebral disc degeneration treatment through various mechanisms. These mechanisms include mitigating cell loss and senescence, delaying extracellular matrix degeneration, and modulating the inflammatory microenvironment. Additionally, it highlights recent efforts in engineering extracellular vesicles to enhance their targeting and therapeutic efficacy. The integration of extracellular vesicle-based acellular therapy is anticipated to drive significant advancements in disc regenerative medicine.</div></div><div><h3>The translational potential of this article</h3><div>Existing clinical treatment strategies often fail to effectively address the challenges associated with regenerating degenerated intervertebral discs. As a new regenerative medicine strategy, the extracellular vesicle strategy avoids the risks associated with cell transplantation and shows great promise in treating intervertebral disc degeneration by carrying therapeutic cargo. This review comprehensively examines the latest research, underlying mechanisms, and therapeutic potential of extracellular vesicles, offering a promising new strategy for intervertebral disc degeneration treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 44-55"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047032","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}