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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

Bone research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling Johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany institute of orthopedic research and biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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Skeletal interoception in osteoarthritis

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Bone research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen Xu Ke Xu Peng Xu Department of Joint Surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China Department of orthopedic Surgery and orthopedic research institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

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Experimental study on boundary lubricity of superficial area of articular cartilage and synovial fluid

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Friction 2024年第5期12卷 981-996页

作者： Wenxiao LI Takehiro MORITA Yoshinori SAWAE Departure of Mechanical Engineering Kyushu UniversityFukuoka8190395Japan International institute for Carton-Neutral Energy research Kyushu UniversityFukuoka8190395Japan Advanced research Center for biomechanics Kyushu UniversityFukuoka8190395Japan

The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in *** this study,to elucidate the lubricating function of the superficial area of articular cartilage and synovial fluid(SF),cartilage specimens were processed with four different treatments:gentle and severe washing with detergent,incubation in NaCl solution,and trypsin digestion to selectively remove certain constituents from the cartilage ***,the frictional characteristics were examined in phosphate-buffered saline(PBS)and SF against *** reciprocating sliding tests with a spherical glass probe and square articular cartilage specimens were performed at low contact loads in the mN range to extract the frictional behavior in the superficial area of the cartilage ***,the cartilage surface was observed to confirm the effects of treatments on the morphology of the cartilage surface using a fluorescence microscope and water-immersion *** coefficient of friction(COF)of the prepared cartilage specimens was varied from 0.05 to over 0.3 in ***,a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited *** the low COF group of specimens,all four treatments increased the COF in PBS to different extents,and fluorescence microscopy revealed that the integrity of the cartilage surface was deteriorated by *** means that the intact cartilage surface had lubricating constituents to maintain low friction,and the removal of such constituents resulted in the loss of the intrinsic boundary lubricity of the cartilage *** variation in the COF of the cartilage specimens was suppressed in SF because it had a clear boundary lubrication effect on the cartilage *** lubricating effect of SF could be confirmed even after degenerative treatment.

关键词： articular cartilage synovial fluid the uppermost superficial layer boundary lubrication

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Sema3A secreted by sensory nerve induces bone formation under mechanical loads

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International Journal of Oral Science 2024年第1期16卷 62-72页

作者： Hongxiang Mei Zhengzheng Li Qinyi Lv Xingjian Li Yumeng Wu Qingchen Feng Zhishen Jiang Yimei Zhou Yule Zheng Ziqi Gao Jiawei Zhou Chen Jiang Shishu Huang Juan Li State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of orthopedic Surgery and orthopedic research institute West China HospitalSichuan UniversityChengduChina

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 ***, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

关键词： Sema3A formation overload

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Bioinspired Hollow Mesoporous Silica Nanoparticles Coating on Titanium Alloy with Hierarchical Structure for Modulating Cellular Functions

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Journal of Bionic Engineering 2024年第3期21卷 1427-1441页

作者： Jiaxin Zhang He Liu Jincheng Wang Jing Shang Mingwei Xu Xiujie Zhu Chao Xu Haotian Bai Xin Zhao orthopedic institute of Jilin Province Orthopedic Medical CenterThe Second Hospital of Jilin UniversityChangchun130041China Key Laboratory of Bionic Engineering(Ministry of Education) Jilin UniversityChangchun130025China institute of Structured and Architected Materials Liaoning Academy of MaterialsShenyang110167China

3D-printed Porous Titanium Alloy Implants(pTi),owing to their biologically inertness and relatively smooth surface morphology,adversely affect the biological functions of surrounding *** address the challenges,constructing a bioinspired interface that mimics the hierarchical structure of bone tissue can enhance the cellular functions of *** this context,Hollow Mesoporous Silica Nanoparticles(HMSNs),renowned for their unique physicochemical properties and superior biocompatibility,offer a promising direction for this *** this research,the initially synthesized HMSNs were used to construct a“hollow-mesoporous-macroporous”hierarchical bioinspired coating on the pTi surface through the Layer-by-Layer ***,diverse morphologies of coatings were established by adjusting the deposition strategy of PDDA/HMSNs on the pTi surface(pTi-HMSN-2,pTi-HMSN-4,pTi-HMSN-6).A range of techniques were employed to investigate the physicochemical properties and regulation of cellular biological functions of the diverse HMSN coating ***,the pTi-HMSN-4 and pTi-HMSN-6 groups exhibited the uniform coatings,leading to a substantial enhancement in surface roughness and ***,the coating constructed strategy of pTi-HMSN-4 possessed commendable *** on the aforementioned findings,both pTi-HMSN-4 and pTi-HMSN-6 facilitated the adhesion,spreading,and pseudopodia extension of BMSCs,which led to a notable upsurge in the expression levels of vinculin protein in *** analysis indicates that the coating,when PDDA/HMSNs are deposited four times,possesses favorable overall *** research will provide a solid theoretical basis for the translation of HMSN bioinspired coatings for orthopedic implants.

关键词： Hollow mesoporous silica nanoparticles Bioinspired coating Titanium alloy Hierarchical structure Cellular functions

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Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States

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World Journal of orthopedics 2024年第8期15卷 754-763页

作者： Mahad M Hassan Aliya G Feroe Brenton W Douglass Andrew E Jimenez Benjamin Kuhns Charles F Mitchell Robert L Parisien Daniel A Maranho Eduardo N Novais Young-Jo Kim Ata M Kiapour Department of orthopedic Surgery University of MinnesotaMinneapolisMN 55454United States Department of orthopedic Surgery TRIA Orthopaedic CenterBloomingtonMN 55122United States Department of orthopedic Surgery Boston Children’s HospitalBostonMA 02115United States Department of orthopedic Surgery Mayo ClinicRochesterMN 55901United States Department of Orthopaedics and Rehabilitation Yale School of MedicineNew HavenCT 06510United States Department of orthopedic Surgery American Hip Institute Research FoundationDes PlainesIL 60018United States Department of orthopedic Surgery Mount SinaiNew YorkNY 10029United States Department of biomechanics Medicineand Rehabilitation of the Locomotor SystemRibeirao Preto Medical SchoolUniversity of São PauloRibeirao Preto 14048-900São PauloBrazil

BACKGROUND The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular *** To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric *** hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both *** Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States(8-18 years;50%male)without hip *** femoral measurements including the femoral head diameter,femoral head volume,residual volume,asphericity index,and local diameter difference were used to evaluate femoral head *** In both sexes,the residual volume increased by age(P13 years)in females,there were no sex-differences in residual volume and aspherity *** were no age-related changes in mean diameter difference in both sexes(P=0.07)with no significant sex-differences across different age groups(P=0.06).In contrast,there were significant increases in local aspherity(maximum diameter difference)across whole surface of the femoral head and all quadrants except the inferior regions in males(P=0.03).There were no sex-differences in maximum diameter difference at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head(P=0.024).CONCLUSION There is a substantial localized asphericity in asymptomatic hips which increases with age *** 2D measured alpha angle can capture overall asphericity of the femoral head,it may not be sensitive enough to represent regional asphericity patterns.

关键词： Hip Femoral head Sphericity Skeletal growth Sex differences

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Glycerol solutions of highly concentrated biomineral counter-ions towards water-responsive mineralization: Demonstration on bacterial cellulose and its application in hard tissue repair

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Nano research 2024年第3期17卷 2154-2163页

作者： Yunfei Zhao Xiaohao Liu Zhi Zhou Chaobo Feng Nan Luo Jiajun Yan Shuo Tan Yang Lu Feng Chen Bing-Qiang Lu Shisheng He Department of orthopedic Spinal Pain Research InstituteShanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai 200011China

Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue *** current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low *** typically results in inefficient mineralization and weak control over biomineral ***,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic *** approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and *** resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy *** shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory *** study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites.

关键词： biomineralization organic solvent bacterial cellulose(BC) hard tissue repair

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A new perspective on intervertebral disc calcification—from bench to bedside

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Bone research 2024年第1期12卷 50-61页

作者： Emanuel J.Novais Rajkishen Narayanan Jose A.Canseco Koen van de Wetering Christopher K.Kepler Alan S.Hilibrand Alexander R.Vaccaro Makarand V.Risbud Department of Orthopaedic Surgery Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaPAUSA Unidade Local de Saúde do Litoral Alentejano Orthopedic DepartmentSantiago do CacémPortugal Rothman orthopedic institute at Thomas Jefferson University PhiladelphiaPAUSA

Disc degeneration primarily contributes to chronic low back and neck ***,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed *** these phenotypes,disc calcification is the least *** calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and ***,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative *** is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local *** studies in mouse models have provided a better understanding of the mechanisms underlying this *** is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP ***,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to ***,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation *** there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

关键词： degeneration metabolism intervertebral

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Optimal search path planning of UUV in battlefeld ambush scene

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Defence Technology（防务技术） 2024年第2期32卷 541-552页

作者： Wei Feng Yan Ma Heng Li Haixiao Liu Xiangyao Meng Mo Zhou Naval research institute Beijing100161China

Aiming at the practical application of Unmanned Underwater Vehicle(UUV)in underwater combat,this paper proposes a battlefield ambush scene with UUV considering ocean ***,by establishing these mathematical models of ocean current environment,target movement,and sonar detection,the probability calculation methods of single UUV searching target and multiple UUV cooperatively searching target are given ***,based on the Hybrid Quantum-behaved Particle Swarm Optimization(HQPSO)algorithm,the path with the highest target search probability is ***,through simulation calculations,the influence of different UUV parameters and target parameters on the target search probability is analyzed,and the minimum number of UUVs that need to be deployed to complete the ambush task is demonstrated,and the optimal search path scheme is *** method proposed in this paper provides a theoretical basis for the practical application of UUV in the future combat.

关键词： Battlefield ambush Optimal search path planning UUV path Planning Probability of cooperative search

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Mesenchymal stem cell-derived exosomes: Versatile nanomaterials for skin wound treatment

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Nano research 2024年第4期17卷 2836-2856页

作者： Yuzhen Xiao Hexi Li Junhui Zhang Songyun Yang Chunsen Zhang Yizhou Huang Xin Tang Huiqi Xie Department of orthopedic Surgery and orthopedic research institute Laboratory of Stem Cell and Tissue EngineeringState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu 610041China West China School of Public Health and West China Fourth Hospital Sichuan UniversityChengdu 610041China Sports Medicine Center West China HospitalSichuan UniversityChengdu 610041China

Accumulating studies reveal that mesenchymal stem cells(MSCs)promote skin wound healing mainly through the paracrine ***,one of the crucial paracrine mediators in wound healing,are cell-derived nanosized membranous vesicles containing diverse bioactive *** the potent ability of modulating skin cell behaviors,MSC-derived exosomes(MSC-Exos)are regarded as a promising nanomaterial for regenerative wound *** hostile conditions,MSC-Exos are efficient in protecting skin cells from severe damage and restoring their *** to recent studies,MSC-Exos possess remarkable pro-healing effects in a variety of skin wounds,typically resulting in increased wound closure,inhibited scar tissue formation,and better restoration of skin *** further enhance the therapeutic potential of MSC-Exos,the development of applicable pretreatment strategies and the optimization of exosome delivery are under intensive ***,we summarize current research progress of MSC-Exos for skin wound treatment,with an emphasis on the biological effects of these nanovesicles,the repair mechanisms,and future challenges in clinical translation.

关键词： exosomes mesenchymal stem cells diabetic wounds burn wounds scar wound healing

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