Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Effects of contact/collision sport history on gait in early-to mid-adulthood

Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged adults.Methods:The study recruited 113 adults(34.88±11.80 years,(mean±SD);53.0%female)representing 4 groups.Groups included(a)former non-contact/collision athletes and non-athletes who are not physically active(n=28);(b)former non-contact/collision athletes who are physically active(n=29);(c)former contact/collision sport athletes who participated in high-risk sports and are physically active(n=29);and(d)former rugby players with prolonged repetitive head impact exposure history who are physically active(n=27).Gait parameters were collected using inertial measurement units during ST and DT gait.DT cost was calculated for all gait parameters(double support,gait speed,and stride length).Groups were compared first using one-way analysis of covariance.Then a multiple regression was performed for participants in the highrisk sport athletes and repetitive head impact exposure athletes groups only to predict gait outcomes from contact/collision sport career duration.Results:There were no significant differences between groups on any ST,DT,or DT cost outcomes(p>0.05).Contact/collision sport duration did not predict any ST,DT,or DT cost gait outcomes.Conclusion:Years and history of contact/collision sport participation does not appear to negatively affect or predict neurobehavioral function in early-to mid-adulthood among physically active individuals.

Update on mesenchymal stem cell therapies for cartilage disorders

Cartilage disorders, including focal cartilage lesions, are among the most common clinical problems in orthopedic practice. Left untreated, large focal lesions may result in progression to osteoarthritis, with tremendous impact on the quality of life of affected individuals. Current management strategies have shown only a modest degree of success, while several upcoming interventions signify better outcomes in the future. Among these, stem cell therapies have been suggested as a promising new era for cartilage disorders. Certain characteristics of the stem cells, such as their potential to differentiate but also to support healing made them a fruitful candidate for lesions in cartilage, a tissue with poor healing capacity. The aim of this editorial is to provide an update on the recent advancements in the field of stem cell therapy for the management of focal cartilage defects. Our goal is to present recent basic science advances and to present the potential of the use of stem cells in novel clinical interventions towards enhancement of the treatment armamentarium for cartilage lesions. Furthermore, we highlight some thoughts for the future of cartilage regeneration and repair and to explore future perspectives for the next steps in the field.

Multi-factorial sustainability approach is necessary to preserve knee function following osteoarthritis diagnosis

Knee function preservation following a diagnosis of osteoarthritis may benefit from healthy patient lifestyles, exercise or activity habits, and daily living routines. Underlying societal issues and social roles may contribute further to both ecological and knee function preservation concerns. Based on sustainability theory and social ecology concepts we propose that factors such as health history, genetic predisposition, socioenvironmental factors and local-regional-global physiological system viability contribute to knee function preservation. Addressing only some of these factors or any one factor in isolation can lead the treating physician, surgeon and rehabilitation clinician to less than optimal treatment effectiveness. An example is presented of a 57-year-old man with medial tibiofemoral osteoarthritic. In the intervention decision-making process several factors are important. Patients who would benefit from early knee arthroplasty tend to place osteoarthritis knee pain elimination at the top of their list of treatment expectations. They also have minimal or no desire to continue impact sport, recreational or vocational activities. In contrast, patients who are good candidates for a knee function preservation treatment approach tend to have greater expectations to be able to continue impact sport, recreational or vocational activities, are willing and better able to implement significant behavioral changes and develop the support systems needed for their maintenance, are willing to tolerate and live with minor-to-moderate intermittent knee pain, and learn to become more pain tolerant.

Impaired eye tracking is associated with symptom severity but not dynamic postural control in adolescents following concussion

Purpose:The purpose of the study was to(1)examine the relationship between self-reported symptoms and concussion-related eye tracking impairments,and(2)compare gait performance between(a)adolescents with a concussion who have normal eye tracking,(b)adolescents with a concussion who have abnormal eye tracking,and(c)healthy controls.Methods:A total of 30 concussed participants(age:14.4±2.2 years,mean±SD,50%female)and 30 controls(age:14.2±2.2 years,47%female)completed eye tracking and gait assessments.The BOX score is a metric of pupillary disconjugacy,with scores<10 classified as normal and≥10 abnormal.Symptoms were collected using the Post-Concussion Symptom Scale(PCSS),and gait speed was measured with triaxial inertial measurement units.We conducted a linear regression to examine the relationship between PCSS and BOX scores and a two-way mixed effects analysis of variance to examine the effect of group(abnormal BOX,normal BOX,and healthy control)on single-and dual-task gait speed.Results:There was a significant association between total PCSS score and BOX score in the concussion group(β=0.16,p=0.004,95%confidence interval(95%CI):0.06‒0.27),but not in the control group(β=0.21,p=0.08,95%CI:0.03 to 0.45).There were no significant associations between PCSS symptom profiles and BOX scores in the concussion or control groups.There were also no significant differences in singletask(Abnormal:1.00±0.14 m/s;Normal:1.11§0.21 m/s;Healthy:1.14±0.18 m/s;p=0.08)or dual-task(Abnormal:0.77±0.15 m/s;Normal:0.84±0.21 m/s;Healthy:0.90±0.18 m/s;p=0.16)gait speed.Conclusion:The concussed group with impaired eye tracking reported higher total symptom severity,as well as worse symptom severity across the 5 PCSS symptom domain profiles.However,eye tracking deficits did not appear to be driven by any particular symptom domain.While not statistically significant,the slower gait speeds in those with abnormal BOX scores may still be clinically relevant since gait-related impairments may persist beyond clinical recovery.

Long noncoding RNAs in mesenchymal stromal/stem cells osteogenic differentiation:Implications in osteoarthritis pathogenesis

This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it discusses a novel modality of epigenetic regulation,the long noncoding RNAs(lncRNAs),and provides evidence of their involvement in mesenchymal stromal/stem cells osteo-/adipogenic differentiation balance.Despite focus on lncRNAs,there is an emerging cross talk between lncRNAs and miRNAs interaction as a novel mechanism in the regulation of the function of the musculoskeletal system,by controlling bone homeostasis and bone regeneration,as well as the osteogenic differentiation of stem cells.Thus,we touched on some examples to demonstrate this interaction.In addition,we believe there is still much to discover from the effects of lncRNAs on progenitor and non-progenitor cell differentiation.We incorporated data from other published articles to review lncRNAs in normal progenitor cell osteogenic differentiation,determined lncRNAs involved in osteoarthritis pathogenesis in progenitor cells,and provided a review of lncRNAs in non-progenitor cells that are differentially regulated in osteoarthritis.In conclusion,we really enjoyed reading this article and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.

Case Study: EIMS Acupuncture Treatment for Posterior Tibialis Tendonitis

BACKGROUND AND OBJECTIVE: Posterior tibialis tendon dysfunction (PTTD) is a progressive ailment of a lower limb that, if left untreated, can lead to irreversible changes in the structure and function. The authors of the present study hypothesized the damages to the tibias tendon can be countered and reversed using electrical acupuncture and concurrent treatment of the associated muscle. INTERVENTION: The following study details a successful treatment of the early stage PTTD in a group of competitive athletes using a specific Electrical Intra Muscular Stimulation (EIMS) protocol developed and rooted in years of practice and the knowledge of the pathophysiology of the muscle and tendon tissues. Specifically, a combination the posterior and the original EIMS approach was used to stimulate the tendon and muscle concurrently at a frequency of 2 Hz. Analysis of the VAS scores showed a significant improvement following the treatment sessions. CONCLUSION: The success of this combined muscle/tendon stimulation protocol is given a strong correlation between the mechanism of tendon and muscle injury and recovery. The fast rate of healing and the simplicity of the materials required for the treatment offer a great potential for a wide-spread application. The authors extrapolate that the treatment method, with applicable modifications in needling locations, can be used for an array of common ailments involving tendons and muscles of the lower limb and foot, including the over-pronation, which is now common place due to the overweight problem in the general population.

Cholinergic dysfunction-induced insufficient activation of alpha7 nicotinic acetylcholine receptor drives the development of rheumatoid arthritis through promoting protein citrullination via the SP3/PAD4 pathway

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis(RA),but the relationship between the two phenomena remains unclear.We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA.Cholinergic function and protein citrullination levels in patients with RA and collageninduced arthritis(CIA)mice were collected.In both neuron-macrophage coculture system and CIA mice,the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases(PADs)was assessed by immunofluorescence.The key transcription factors for PAD4 expression were predicted and validated.Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues.The cholinergic or alpha7 nicotinic acetylcholine receptor(a7nAChR)deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo,respectively.Especially,the activation deficiency of a7nAChR induced the earlier onset and aggravation of CIA.Furthermore,deactivation of a7nAChR increased the expression of PAD4 and specificity protein-3(SP3)in vitro and in vivo.Our results suggest that cholinergic dysfunction-induced deficient a7nAChR activation,which induces the expression of SP3 and its downstream molecule PAD4,accelerating protein citrullination and the development of RA.

Fish scale-derived scaffolds with MSCs loading for photothermal therapy of bone defect

Tissue engineering scaffolds have presented effective value in bone repair.However,the integration of the diverse components,complex structures,multifunction to impart the scaffolds with improved applicability is still a challenge.Here,we propose a novel fish-derived scaffold combined with photothermal therapy and mesenchymal stem cells(MSCs)to promote bone regeneration.The fish-derived scaffold is composed of the decellularized fish scale and gelatin methacrylate synthesized from fish gelatin(fGelMA),which can promote the proliferation and osteogenesis of MSCs with no obvious immunological rejection.Furthermore,the black phosphorus(BP)nanosheets are incorporated into the fGelMA hydrogel network,which can endow the hydrogel with the capacity of photothermal conversion stimulated by near-infrared(NIR)light.The fish-derived scaffold can promote the osteogenesis process of MSCs with higher expression of osteogenic markers and higher mineralization assisted by the NIR light in vitro.The regeneration of mice calvarial defect has also been accelerated by the scaffold with photothermal therapy and MSCs.These results suggest that the fish-derived scaffold,photothermal therapy,MSCs-based regenerative therapy is a promising clinical strategy in bone regeneration.

Pornography use among adolescents and the role of primary care

Given the increase in pornography use among adolescents over the years,we discuss the impact of its use on sexual health development as well as the role of primary care providers(PCPs)in assessing use and providing sexual health education.While pornography use is often viewed negatively,it is important to develop unbiased understanding of the use in order to provide non-judgemental,adolescent-focused and educational care.As PCPs are often the first point of contact when adolescents experience medical and behavioural health concerns,it is essential for them to be equipped to screen for pornography use effectively,create a confidential and comfortable environment to talk about pornography use and sexuality,and be informed of ways to promote open discussion between youth and parents.In addition to PCP involvement,parental collaboration,knowledge and comfortability with discussing pornography use with their child are powerful tools in understanding and navigating pornography use in this population.This special communication seeks to provide an objective view of adolescents’pornography use,guidelines for screening of pornography use and ways to facilitate conversations about the use between adolescents and caregivers.

Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

The Influence of Biological Maturity on Dynamic Force-Time Variables and Vaulting Performance in Young Female Gymnasts

Purpose This cross-sectional study investigated dynamic force-time variables and vaulting performance in young female gymnasts of different maturity status.Methods 120 gymnasts aged 5-14 years were sub-divided into maturity groupings using percent of predicted adult height(%PAH)attained.Participants performed three jumping protocols,the squat jump(SJ),countermovement jump(CMJ)and drop jump(DJ),before completing straight jump vaults that were recorded using two-dimensional video.Results Jumping performance improved with biological maturity evidenced by the most mature gymnasts’producing sig-nificantly more absolute force(P<0.05;all d>0.78),impulse(P<0.05;all d>0.75)and power(P<0.05;all d>0.91)than the least mature group,resulting in the greater jump heights(P<0.05;all d>0.70).While,no significant differences were observed in relative peak force across multiple tests,measures of relative peak power did significantly increase with maturity.Based upon regression analyses,maturation was found to influence vertical take-off velocity during vaulting,explaining 41%of the variance in each jumping protocol.Across all tests,the DJ was found to have the highest predictive ability of vaulting vertical take-off velocity,explaining 55%of the total variance.Conclusion Biological maturation impacts jump height and underpinning mechanical variables in young female gymnasts.Vaulting vertical take-off velocity appears to be influenced by maturation and various dynamic force-time variables,par-ticularly those during DJ,which had the highest explained total variance.

Targeted Application of Motor Learning Theory to Leverage Youth Neuroplasticity for Enhanced Injury-Resistance and Exercise Performance: OPTIMAL PREP

Youth athletes are ideal candidates for novel therapeutic motor learning interventions that leverage the plasticity of the central nervous system to promote desirable biomechanical adaptions.We summarize the empirical data supporting the three pillars of the Optimizing Performance Through Intrinsic Motivation and Attention for Learning(OPTIMAL)theory of motor learning and expand on potential neurophysiologic mechanisms that will support enhanced movement mechan-ics in youth to optimize prevention programs for reduced injury risk,injury rehabilitation,exercise performance,and play(Prevention Rehabilitation Exercise Play;PREP).Specifically,we highlight the role of motivational factors to promote the release of dopamine that could accelerate motor performance and learning adaptations.Further,we detail the potential for an external focus of attention to shift attentional allocation and increase brain activity in regions important for sensorimotor integration to facilitate primary motor cortex efficiency.This manuscript serves to provide the most current data in support of the application of OPTIMAL PREP training strategies of the future.

Utility of Kinetic and Kinematic Jumping and Landing Variables as Predictors of Injury Risk: A Systematic Review

Purpose Jump-landing assessments provide a means to quantify an individual’s ability to attenuate ground reaction forces,generate lower limb explosive power and maintain joint alignment.In order to identify risk factors that can be targeted through appropriate training interventions,it is necessary to establish which(scalar)objective kinetic,kinematic,and performance measures are most associated with lower-extremity injury.Methods Online searches of MEDLINE,SCOPUS,EBSCOHost,SPORTDiscus and PubMed databases were completed for all articles published before March 2020 in accordance with PRISMA guidelines.Results 40 articles investigating nine jump-landing assessments were included in this review.The 79%of studies using drop jump(n=14)observed an association with future injury,while only 8%of countermovement jump studies(n=13)observed an association with injury risk.The 57%of studies using unilateral assessments found associations with risk of injury(n=14).Studies using performance measures(jump height/distance)as outcome measure were only associated with injury risk in 30%of cases.However,those using kinetic and/or kinematic analyses(knee abduction moment,knee valgus angle,knee separation distance,peak ground reaction force)found associations with injury in 89%of studies.Conclusion The landing element of jump-landing assessments appears to be superior for identifying individuals at greater risk of injury;likely due to a closer representation of the injury mechanism.Consequently,jump-landing assessments that involve attenuation of impact forces such as the drop jump appear most suited for this purpose but should involve assessment of frontal plane knee motion and ground reaction forces.

Bone microenvironment regulative hydrogels with ROS scavenging and prolonged oxygen-generating for enhancing bone repair

Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration.However,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells.Therefore,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair.Herein,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogel”to reverse the hypoxic microenvironment in bone defects region.CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase(CAT)and ROS-responsive oxygen-releasing nanoparticles(PFC@PLGA/PPS)co-loaded liposome(CCP-L)and GelMA hydrogels.Under hypoxic condition,CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks.The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis.Finally,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway.Hence,CPP-L/GelMA,as a bone microenvironment regulative hydrogel for bone tissue respiration,can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region,possessing of great clinical therapeutic potential.

3D-printed fish gelatin scaffolds for cartilage tissue engineering

Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment of osteoarthritis challenging.Here,we present a three-dimensional(3D)printed porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage regeneration.To make the scaffold,cold-water fish skin gelatin was combined with sodium alginate to increase viscosity,printability,and mechanical strength,and the hybrid hydrogel was printed according to a pre-designed specific structure using 3D printing technology.Then,the printed scaffolds underwent a double-crosslinking process to enhance their mechanical strength even further.These scaffolds mimic the structure of the original cartilage network in a way that allows chondrocytes to adhere,proliferate,and communicate with each other,transport nutrients,and prevent further damage to the joint.More importantly,we found that cold-water fish gelatin scaffolds were nonimmunogenic,nontoxic,and biodegradable.We also implanted the scaffold into defective rat cartilage for 12 weeks and achieved satisfactory repair results in this animal model.Thus,cold-water fish skin gelatin scaffolds may have broad application potential in regenerative medicine.

Cerium oxide nanozymes alleviate oxidative stress in tenocytes for Achilles tendinopathy healing

Background:Reactive oxygen species(ROS)is considered as ubiquitous and highly active chemicals that influence tendon integrity and orchestrate tendon repair.With significant recent advances in nanomaterials,cerium oxide nanoparticles(CeO_(2)NPs)exhibit superoxide dismutase-and catalase-like activities.Herein,we introduced a therapeutic approach of CeO_(2)NPs for Achilles tendinopathy(AT)healing.Methods:CeO_(2)NPs were synthesized to examine their effect as ROS scavengers on AT healing in vitro and in vivo.The mRNA levels of inflammatory factors were evaluated in AT after CeO_(2)NPs treatment in vitro.The mechanisms underlying CeO_(2)NPs-mediated stimulation of NRF2 translocation and ERK signaling were verified through immunofluorescence and Western blot analysis.The efficacy of CeO_(2)NPs was tested in an AT rat model in comparison with the control.Results:CeO_(2)NPs not only significantly scavenged multiple ROS and suppressed ROS-induced inflammatory reactions but also protected cell proliferation under oxidative stress induced by tert-butyl hydroperoxide(TBHP).Moreover,CeO_(2)NPs could promote NRF_(2)nuclear translocation for anti-oxidation and anti-inflammation through the ERK signaling pathway.In a rat model of collagenase-induced tendon injuries,CeO_(2)NPs showed significant therapeutic efficacy by ameliorating tendon damage.Conclusion:The present study provides valuable insights into the molecular mechanism of CeO_(2)NPs to ameliorate ROS in tenocytes via the ERK/NRF_(2)signaling pathway,which underscores the potential of CeO_(2)NPs for application in the treatment of enthesopathy healing.

Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheumatoid arthritis via regulating inflammatory environment

Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.

Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis

Osteoporosis is the most common degenerative orthopedic disease in the elderly.Recently,the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues,which could provide a suitable environment for the positive regulation of bone metabolism,promoting osteogenic differentiation and inhibiting osteoclast differentiation.Our previous work demonstrated that iron oxide nanoparticles(IONPs)could positively regulate bone metabolism in vitro.In this study,we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo.Meanwhile,IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice.Besides,alendronate,a clinically used anti-osteoporosis bisphosphate,was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role.Eventually,we verified the bone targeting ability,therapeutic efficiency,and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice.By applying BTNPs,the OVX-induced osteoporosis was significantly revised in mice models via the positive regulation of bone metabolism.