Journal of Orthopaedic Translation最新文献

{"title":"Tirzepatide, a dual GLP-1 and GIP receptor agonist, promotes bone loss in obese mice via gut microbial-related metabolites","authors":"Ning Chen , Mengdan Zhang , Baohong Shi , Xiumei Luo , Rui Huang , Zhengqiong Luo , Junliang He , Shengye Xue , Na Li , Zemin Ling , Hao Guo , Ren Xu , Yuejun Liu","doi":"10.1016/j.jot.2025.09.002","DOIUrl":"10.1016/j.jot.2025.09.002","url":null,"abstract":"<div><h3>Background</h3><div>As a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, Tirzepatide (TZP) is a recently approved medication for treating type 2 diabetes mellitus (T2DM) and obesity; however, the effect of TZP in bone remodeling remains unclear.</div></div><div><h3>Methods</h3><div>1. The effect of Tirzepatide on osteoblasts and osteoclasts was observed by inducing differentiation of bone marrow mesenchymal cells (BMSCs) <em>in vitro</em>. 2. Db/db mice were used as a pathological model to investigate the role of TZP on bone metabolism. After TZP intervention, the feces in the intestinal tract of mice were collected for 16s rRNA gene sequencing to select the candidate gut microbiota most related to bone mass, and the effects of gut microbiota on bone metabolism were verified through subsequent microbiota supplementation experiments. 3. Metabolomics was used to analyze the difference of fecal metabolites between mice with the candidate microbiota supplement and those without, and the effect of candidate metabolites on bone metabolism was verified by the <em>in vitro</em> intervention of differential metabolites in BMSCs induction differentiation experiments.</div></div><div><h3>Results</h3><div>We found that TZP intervention resulted in a significant decrease in bone mass accrual <em>in vivo</em>. TZP was not indispensable to the differentiation of osteoblasts and osteoclasts <em>in vitro</em>. Bone and fat homeostasis were modulated by gut microbiota. We further demonstrated that the biodiversity of the gut microbiota in db/db mice was strikingly altered after TZP treatment. <em>Lachnospiraceae</em>, a key pro-osteogenic component of gut microbiota was significantly reduced. As a main metabolite of <em>Lachnospiraceae</em>, evodiamine played a role in suppressing osteoclastogenesis <em>in vitro</em>. Based on this, the transplantation of the <em>Lachnospiraceae</em> effectively ameliorated bone loss that was seen in db/db mice due to TZP treatment.</div></div><div><h3>Conclusion</h3><div>TZP administration leads to bone loss in the context of diabetes and obesity, and targeting the composition of gut microbiota may provide a potential way to protect bone health in type 2 diabetic patients treating with TZP.</div></div><div><h3>The translational potential of this article</h3><div>This study indicates that TZP has a negative impact on bone mass, suggesting that clinical attention should be paid to the risk of further decline in bone mass after Tirzepatide treatment, and it is necessary to follow up on their bone metabolism. Additionally, the gut microbiota plays an important role in bone metabolism regulation, and supplementing with certain probiotics may have a preventive effect on bone mass reduction associated with TZP treatment. Our research provides a reference for the prevention and treatment of drug-related osteoporosis in patients with T2DM in the future.</div></di","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 280-292"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220803","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":"Hydrogel adhesives with a hydrodynamically induced liquid–solid transition for annular fissure sealing and inflammation modulation following microdiscectomy","authors":"Huan Wang ,&nbsp;Moyan Li ,&nbsp;Jiaojiao Yang ,&nbsp;Zhao Liu ,&nbsp;Shijie Shi ,&nbsp;Dachuan Liu ,&nbsp;Youzhi Hong ,&nbsp;Hongjian Liu ,&nbsp;Songfeng Chen ,&nbsp;Jiyao Li ,&nbsp;Song Chen ,&nbsp;Bin Li","doi":"10.1016/j.jot.2025.08.004","DOIUrl":"10.1016/j.jot.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc (IVD) herniation is a major cause of low back pain and disability, with microdiscectomy being the standard surgical treatment. However, microdiscectomy fails to address annulus fibrosus (AF) defects, increasing the risk of recurrent herniation. Current therapeutic strategies for this condition remain limited in efficacy. The lack of repair following injury and unresolved inflammation can further damage the IVD function, ultimately leading to irreversible IVD degeneration. Therefore, the development of an AF adhesive capable of both mechanically stabilizing annular fissures and enabling localized anti-inflammatory drug delivery emerges as a promising strategy to address this clinical challenge.</div></div><div><h3>Methods</h3><div>The developed AF adhesive system, designated as STIG, is formulated from silk fibroin, tannic acid, ibuprofen, and guanidine hydrochloride (GuCl). A comprehensive evaluation is conducted on STIG, encompassing its microstructure, composition, injectability, tissue adhesion, rheological properties, and biocompatibility. To assess anti-inflammatory efficacy, an <em>in vitro</em> inflammatory microenvironment is established via lipopolysaccharide (LPS)-stimulated AF cells. For <em>in vivo</em> validation, a rat model of IVD degeneration is surgically induced through puncturing the AF to simulate nucleus pulposus (NP) herniation. This experimental framework enables evaluation of STIG's ability to prevent NP protrusion, modulate inflammatory responses, and delay IVD degeneration.</div></div><div><h3>Results</h3><div>In the STIG system, GuCl serves the role of a hydrogen bond disruptor, facilitating its release into bodily fluids, which in turn allows for the reformation of hydrogen bonds. This property endows STIG with the ability to transition from an injectable, low-stiffness state to a high-stiffness adhesive gel upon contact with water. The inclusion of ibuprofen in the adhesive effectively curbs the production of inflammatory mediators and the breakdown of extracellular matrix constituents. In a rat tail model, STIG effectively preserves the NP water content, maintains the disc height index, and safeguards the structural integrity of the IVD post-surgery.</div></div><div><h3>Conclusion</h3><div>These findings highlight STIG's potential as a promising therapeutic solution for sealing AF fissures and preventing IVD degeneration.</div></div><div><h3>The translational potential of this article</h3><div>STIG shows significant clinical potential in spinal surgery. It offers a novel approach to reduce the recurrence rate post-microdiscectomy and improving long-term patient outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 62-74"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912730","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":"Upregulation of ACSL1 in synovial macrophages promotes lipid peroxidation via the IκB/NF-κB pathway to accelerate osteoarthritis","authors":"Zihao Yao ,&nbsp;Zhikun Yuan ,&nbsp;Yanhui Li ,&nbsp;Xuming Li ,&nbsp;Changgui Peng ,&nbsp;Junyu Jin ,&nbsp;Haiyan Zhang ,&nbsp;Xiaochun Bai ,&nbsp;Jianying Pan ,&nbsp;Daozhang Cai","doi":"10.1016/j.jot.2025.04.016","DOIUrl":"10.1016/j.jot.2025.04.016","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Osteoarthritis (OA) is a globally prevalent degenerative joint disease, characterized by cartilage degradation and synovial inflammation. Increasing evidence suggests that macrophages in the synovium play a pivotal role in OA pathogenesis. Energy metabolism reprogramming has emerged as a key regulator of macrophage activation in inflammatory diseases. Long-chain fatty acid-CoA ligase 1 (ACSL1), an enzyme critical for lipid metabolism, has been implicated in various diseases. However, the specific mechanism by which ACSL1 regulates macrophage polarization and contributes to OA progression remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this study, we examined ACSL1 expression in the hyperplastic synovium of patients with knee OA and in a mouse model of OA induced by destabilization of the medial meniscus (DMM). We isolated bone marrow-derived macrophages (BMDMs) from C57 mice and transfected them with ACSL1 knockdown plasmids to assess the impact of ACSL1 on macrophage polarization and inflammatory cytokine release. We also investigated the effect of ACSL1 knockdown on cartilage degradation using BMDM supernatant in cartilage explant cultures. Intra-articular injection of AAV-shACSL1 was performed to evaluate its effect on OA progression in a trauma-induced mouse model. The expression of ACSL1, inflammatory cytokines (IL-1, IL-6, TNF-α), and lipopolysaccharide (LPS)-induced macrophage polarization markers (M1 and M2 markers) was assessed using qRT-PCR, Western blotting, and ELISA. Lipid peroxidation and the activation of the IκB/NF-κB signaling pathway were examined to elucidate the mechanism by which ACSL1 regulates inflammation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We observed increased ACSL1 expression in both the hyperplastic synovium of OA patients and the synovium of DMM-induced OA mice. Knockdown of ACSL1 in macrophages inhibited M1 polarization and reduced the release of key inflammatory cytokines, including IL-1, IL-6, and TNF-α. Furthermore, supernatants from ACSL1-knockdown BMDMs mitigated cartilage degradation in explant cultures. Intra-articular injection of AAV-shACSL1 reduced OA progression in a mouse model of trauma-induced OA. Mechanistically, ACSL1 knockdown alleviated LPS-induced inflammation by inhibiting lipid peroxidation and reducing the activation of the IκB/NF-κB pathway, a major regulator of inflammatory responses in macrophages.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;ACSL1 plays a crucial role in regulating the inflammatory state of synovial macrophages in OA. By modulating macrophage polarization and lipid peroxidation, ACSL1 contributes to the progression of OA. Targeting ACSL1 could provide a novel therapeutic strategy for the prevention and treatment of OA.&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 study highlights the pivotal role of ACSL1 in regulating macrophage-mediated inflammation in OA. Targeting ACSL1 expression or its associated path","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 360-375"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786636","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":"Corrigendum to ‘N6-methyladenosine and intervertebral disc degeneration: Advances in detection and pathological insights’ [J Orthop Translat 53 (2025) 38–51/JOT 941]","authors":"Bin Liu ,&nbsp;Guanhui Song ,&nbsp;Yaosheng Wang ,&nbsp;Changheng Song ,&nbsp;Yiping Cao ,&nbsp;Jinlin Tong ,&nbsp;Yuyao Wang ,&nbsp;Xinrong Fan ,&nbsp;Nannan Shi ,&nbsp;Hongyan Zhao ,&nbsp;Danping Fan","doi":"10.1016/j.jot.2025.06.018","DOIUrl":"10.1016/j.jot.2025.06.018","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Page 379"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786638","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":"LOXL2 alleviates post-traumatic knee osteoarthritis and pain","authors":"Faiza Ali ,&nbsp;Rajnikant Dilip Raut ,&nbsp;Chumki Choudhury ,&nbsp;Amit Kumar Chakraborty ,&nbsp;Cheyleann Del Valle-Ponce De Leon ,&nbsp;Pushkar Mehra ,&nbsp;Manish V. Bais","doi":"10.1016/j.jot.2025.08.016","DOIUrl":"10.1016/j.jot.2025.08.016","url":null,"abstract":"<div><h3>Background</h3><div>Cartilage has limited potential for self-regeneration, and damage results in structural, molecular, and functional aberrations, leading to osteoarthritis (OA). Traumatic knee injuries can also lead to cartilage degeneration and post-traumatic OA (PTOA). This study aimed to explore whether lysyl oxidase-like 2 (LOXL2) deletion aggravate PTOA and overexpression alleviate inflammation and pain at mechanical as well as molecular levels.</div></div><div><h3>Methods</h3><div>Modified medial meniscectomy was performed on C57BL/6J mice knee followed by aggrecan promotes specific deletion of <em>Loxl2</em> in cartilage. Transcriptomic aberrations were studied using RNA-seq and qPCR, and biomechanics and allodynia was evaluated using treadmill exhaustion and von Frey nociception test after adenovirus-delivered LOXL2 intra-articular treatment.</div></div><div><h3>Results</h3><div>LOXL2 was found to be downregulated in mouse knee PTOA. <em>Loxl2</em> deletion in knee cartilage, shows OA-like molecular changes, and aggravates PTOA. Transcriptomics analysis revealed the upregulation of cartilage degeneration factors, signatures of inflammatory M1 macrophages, and pain. These <em>Loxl2</em> deleted PTOA mice have a molecular resemblance to the human knee OA pathogenic gene signature. Interestingly, LOXL2 treatment alleviates knee joint function, reduces M1 macrophage infiltration, restores biomechanic capabilities, and reduces mechanical allodynia by relieving knee joint disability and pain.</div></div><div><h3>Conclusion</h3><div>LOXL2 deletion enhances the severity of PTOA, similar to human OA, whereas overexpression mitigates these effects by reducing inflammation and pain, offering LOXL2 as a therapeutic option in OA.</div></div><div><h3>The translational potential of this article</h3><div>LOXL2 modulates inflammation, pain, and degeneration, showing strong translational potential as a disease-modifying therapy for human PTOA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 159-171"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045685","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":"Multi-scale biomimetic fusion construction of cerium ion hydrogel-scaffold for promoting osteoporotic bone defect repair","authors":"Yesheng Jin ,&nbsp;Shuqing Lv ,&nbsp;Nanning Lv ,&nbsp;Yixue Huang ,&nbsp;Jia Wang ,&nbsp;Yun Xiao ,&nbsp;Xinfeng Zhou ,&nbsp;Yanxia Ma ,&nbsp;Gang Zhao ,&nbsp;Fan He ,&nbsp;Yong Xu","doi":"10.1016/j.jot.2025.08.015","DOIUrl":"10.1016/j.jot.2025.08.015","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The treatment of bone defects in the context of osteoporosis encounters numerous challenges. In the osteoporotic microenvironment, bone resorption outweighs bone formation, impeding the self-repair of bone defect areas. Furthermore, the deterioration of osteogenesis-angiogenesis coupling function at the defect sites and excessive inflammatory responses further complicate the treatment of bone defects. Hence, an improved approach is urgently needed to enhance the treatment of osteoporotic bone defects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Our efficient strategy has developed a multi-scale biomimetic fusion alendronate sodium cerium ion hydrogel scaffold, integrating 3D-printed tricalcium phosphate (TCP) scaffolds, collagen-methacrylate (COMA) hydrogel, and nanoparticles of alendronate sodium cerium ions. &lt;em&gt;In vitro&lt;/em&gt;, we intervened osteoporosis rat derived bone marrow stromal cells (BMSCs) with the extract of TCP-H-Alendronate sodium cerium ion nanoparticles (ACNP) scaffold and detected the osteogenesis-related indicators through alkaline phosphatase (ALP) enzymatic activity staining, alizarin red staining, Western Blot, RT-qPCR and immunofluorescence staining to evaluate the osteogenic differentiation effect of TCP-H-ACNP scaffold. Through transcriptome sequencing, we explored the mechanism of TCP-H-ACNP scaffold affecting osteogenic differentiation of osteoporotic BMSCs. We intervened human umbilical vein endothelial cells (HUVECs) with the extract of TCP-H-ACNP scaffold and evaluated the angiogenic effect of TCP-H-ACNP scaffold through tube formation assay and cell scratch assay. &lt;em&gt;In vivo&lt;/em&gt;, we established a distal femoral bone defect model in osteoporotic rats and evaluated the therapeutic effect &lt;em&gt;in vivo&lt;/em&gt; through Mirco CT, Hematoxylin and Eosin (H&amp;E) stainin, Masson staining and immunohistochemical staining.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The results demonstrated that &lt;em&gt;in&lt;/em&gt; &lt;em&gt;vitro&lt;/em&gt;, TCP-H-ACNP scaffolds could promote osteogenic differentiation of osteoporotic BMSCs from rats and angiogenesis of HUVECs. &lt;em&gt;In vivo&lt;/em&gt;, TCP-H-ACNP scaffolds could promote bone regeneration and repair of distal femoral bone defects in osteoporotic rats and improve local angiogenesis. Mechanistically, TCP-H-ACNP scaffolds could directly promote osteogenic differentiation of osteoporotic BMSCs from rats through the Wnt signaling pathway, and indirectly promote osteogenic differentiation by influencing Ca ion transport and improving mitochondrial function.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;We create a hydrogel scaffold that not only offers adequate mechanical support but also possesses a favorable microenvironment for cell growth and contains biological factors promoting osteogenic and angiogenic differentiation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this paper&lt;/h3&gt;&lt;div&gt;This application represents a pioneering aspect of multi-scale biomimetic hydrogel scaffolds in addressing o","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 172-191"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045684","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":"Redefining orthopaedic translation: Harnessing multi-omics, smart biomaterials, and regenerative immunomodulation","authors":"Muhammad Umar ,&nbsp;Di Chen","doi":"10.1016/j.jot.2025.11.001","DOIUrl":"10.1016/j.jot.2025.11.001","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages A1-A3"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786639","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":"3D bioprinting bone/cartilage organoids: construction, applications, and challenges","authors":"Deju Gao ,&nbsp;Ruipeng Li ,&nbsp;Jie Pan ,&nbsp;Cairong Li ,&nbsp;Wei Zhang ,&nbsp;Ling Qin ,&nbsp;Yuxiao Lai","doi":"10.1016/j.jot.2025.08.008","DOIUrl":"10.1016/j.jot.2025.08.008","url":null,"abstract":"<div><div>Orthopaedic disorders, such as osteoporosis and osteoarthritis, impose substantial suffering upon an increasing population, driving demand for accurate disease models. Bone/cartilage organoids offer a promising solution by replicating complex 3D microstructures and multi-cellular niches, overcoming limitations of 2D models and animal experiments. 3D bioprinting, an additive manufacturing technology, enables the spatially precise deposition of cells and bioactive materials, facilitating efficient construction of organoids with enhanced structural fidelity. Therefore, this review specifically focuses on bone and cartilage organoids constructed using 3D bioprinting technologies. We summarize the prevailing 3D bioprinting techniques and biomaterials employed, critically analyze the unique advantages of bioprinting for creating these organoids, explore current technical challenges, such as standardization and scalability, and discuss future research directions. By addressing current progress and key issues in bioprinting bone/cartilage organoids, this review aims to accelerate their standardization and application as powerful platforms for multiscale disease modeling, drug screening, and regenerative medicine strategies. The translational potential of this article: Bone/cartilage organoids constructed via 3D bioprinting, through precise recapitulation of bone and cartilage tissue microenvironment and physiology, enable multiscale disease modeling from localized pathologies to systemic responses, despite persisting unresolved challenges in reproducibility and stability. This review highlights their clinical translational value and elucidates the driven role of 3D bioprinting in accelerating their clinical adoption, particularly in regenerative medicine.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 75-93"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997363","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":"Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases","authors":"Yao Zhang ,&nbsp;Jiale Wang ,&nbsp;Di Hua ,&nbsp;Chunyang Fan ,&nbsp;Wei He ,&nbsp;Yongkang Deng ,&nbsp;Maoting Tang ,&nbsp;Dechun Geng ,&nbsp;Xiexing Wu ,&nbsp;Haiqing Mao","doi":"10.1016/j.jot.2025.08.013","DOIUrl":"10.1016/j.jot.2025.08.013","url":null,"abstract":"<div><div>Degenerative skeletal diseases, including osteoporosis, osteoarthritis, and intervertebral disc degeneration, are prevalent age-related conditions characterized by progressive tissue degeneration and functional decline. Histone modifications are covalent modifications of histone residues, catalyzed by specific enzymes, that modulate chromatin architecture and transcriptional activity. Accumulating evidence highlights the critical involvement of histone modifications in orchestrating disease-associated transcriptional programs. In osteoporosis, histone modifications regulate osteoblast and osteoclast differentiation, thereby disrupting bone homeostasis. In osteoarthritis, they drive the expression of matrix-degrading enzymes in chondrocytes, contributing to cartilage degradation. In intervertebral disc degeneration, they are implicated in nucleus pulposus cell senescence, apoptosis, and extracellular matrix degradation. This review summarizes the distinct mechanistic roles of histone modifications across these conditions and explores the therapeutic potential of targeting histone-modifying enzymes, underscoring epigenetic regulation as a promising strategy for precision intervention in degenerative skeletal diseases.</div><div>The translational potential of this article: This review comprehensively explores the role of histone modifications in degenerative skeletal diseases and evaluates the potential of histone-modifying enzyme inhibitors as therapeutic targets. These insights provide new strategies and directions for the treatment of degenerative skeletal diseases.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 245-266"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096426","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":"Artificial ligaments in anterior cruciate ligament reconstruction: Coating strategies for PET-based materials","authors":"Zhen Peng ,&nbsp;Xinting Feng ,&nbsp;Jiale Tan ,&nbsp;Chunfeng Song ,&nbsp;Laimeng Song ,&nbsp;Yuting Wu ,&nbsp;Lingyi Yuan ,&nbsp;Jiwu Chen","doi":"10.1016/j.jot.2025.08.006","DOIUrl":"10.1016/j.jot.2025.08.006","url":null,"abstract":"<div><div>Artificial ligaments, as an important implant for Anterior Cruciate Ligament reconstruction (ACLR), offer notable advantages in early return to sport. However, most artificial ligaments currently used in clinical ACLR are made of polyethylene terephthalate (PET), a polymer characterized by a smooth and hydrophobic surface that limits cell adhesion and tissue growth, leading to the formation of fibrous scar tissue at the tendon-bone interface. To address these limitations, various surface coating strategies have been developed, including biocompatible, tissue inductive, osteoconductive, drug delivery, and immunomodulatory coatings. These approaches improve biological performance, promote ligamentization, and enhance integration with host tissues. Additionally, the application of composite functional coatings and smart responsive coatings offers new directions for future research. Despite promising preclinical results, most studies remain at the animal experiment stage, and the underlying mechanisms need further investigation. This review summarizes recent advances in coating strategies for artificial ligaments, highlighting their functional classification, technical development, and potential for clinical translation.</div></div><div><h3>Translational potential statement</h3><div>To address key challenges in the application of artificial ligaments, such as limited biocompatibility and poor tissue integration, it is essential to understand the current research progress. This review provides a comprehensive overview of the coatings used for ligaments, highlighting the promising role of surface modification in enhancing implant performance. It offers valuable insights for improving the clinical success rate of artificial ligaments and their long term effectiveness in ACLR, thus holding significant clinical translational potential.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 22-37"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895863","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}