This study aims to develop a novel therapeutic strategy for osteoporosis (OP) by enhancing the osteogenic differentiation potential of mesenchymal stem cells (MSCs). A three-channel biomimetic bone organ-on-a-chip model was constructed. Through bioinformatics analysis, TPD52L1, a key upregulated gene involved in the osteogenic differentiation of MSCs, was identified. Molecular experiments were conducted to verify the effects of its overexpression on the Wnt/β-catenin pathway. Critically, systematic knockdown experiments were performed to validate its necessity in mechanotransduction. Subsequently, functional experiments were performed to evaluate its role in the osteogenic and adipogenic differentiation of MSCs in a GIOP model. Safety assessments for TPD52L1-overexpressing MSCs covered subcellular localization, proliferation, anchorage-independent growth, oncogene expression, and short-term in vivo tumorigenicity. TPD52L1 overexpression activated the Wnt/β-catenin pathway and promoted osteogenic differentiation of MSCs. Its knockdown blocked mechanical stimulation-induced pathway activation and osteogenic marker upregulation, confirming its necessity in mechano-osteogenic conversion. TPD52L1 upregulated osteoblast markers osteocalcin (OCN) and alkaline phosphatase (ALP), downregulated the osteoclast marker tartrate-resistant acid phosphatase (TRAP), and reversed the osteoporosis phenotype. When combined with cyclic mechanical force stimulation in the organ-on-a-chip system, a synergistic effect was observed, enhancing bone repair. TPD52L1 was localized in the cytoplasm, and its endogenous expression was upregulated by mechanical stimulation, indicating mechanosensitivity. TPD52L1 overexpression did not affect MSCs' proliferation, anchorage-independent growth, or oncogene expression. Subcutaneous transplantation experiments confirmed that it did not induce tumor formation or significant pathological changes, demonstrating favorable biosafety. TPD52L1 serves as a key target for promoting the osteogenic differentiation of MSCs.

BackgroundValgus-impacted femoral neck fractures (FNFs) are considered stable fractures in clinical practice. The main surgery approach is closed reduction and internal fixation, particularly in situ fixation. However, several complications commonly occur in healed valgus-impacted FNFs after in situ fixation, such as femoral neck shortening and anterior femoroacetabular impingement, leading to poor functional outcomes. Various closed reduction techniques for valgus-impacted FNFs have been described; however, these methods often involve invasive procedures that carry the risk of vascular damage and infection.MethodHere we present a straightforward non-invasive reduction technique for valgus-impacted FNFs that is easy to perform and effective. This technique achieves reduction through leverage principles without the need for surgical instruments.Result and ConclusionThis approach effectively provides anatomical reduction and may reduce the frequency of complications associated with valgus-impacted FNFs.

Patellar fractures challenge knee function recovery. Traditional tension band wiring (TBW) suffers from K-wire complications and inadequate fracture site compression, prompting modified techniques. We hypothesized that a cerclage-free modified TBW (Group A) would outperform titanium cable TBW (Group B) and titanium cable TBW with cerclage (Group C) in cost, complications, and functional outcomes. In this retrospective study (Level IV evidence), 83 patients (aged 18-80) with unilateral closed transverse patellar fractures (December 2018-2023) were grouped by fixation method. Group A incurred the lowest hospital costs, and Group C had the highest. Operation time was significantly shorter in Group B. However, Groups A and B outperformed Group C in postoperative recovery time, early functional exercise initiation, Lysholm score at 1 year postoperatively, and complication rates. Modified TBW without cerclage demonstrated cost efficiency, reduced complications associated with earlier rehabilitation initiation compared to cerclage-augmented techniques.

Background: The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects. Methods and results: To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors’ results showed that 400 SW pulses at 0.21 mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7. Conclusions: For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.

Background: Patellar fracture is a common injury caused by overstrain of the extensor mechanism or a direct trauma to the knee. The most common complications after patellar fracture are nonunion, infection, post-traumatic arthritis, joint fibrosis, symptomatic hardware, and extensor mechanism failure. These are attributed to the post-fracture flexion and extension movements, the primary damage to the articular cartilage, and the thin soft tissue coverage over the knee. To our knowledge, prepatellar bursa mucosa is an unreported postoperative complication of patellar fracture. Methods: We describe a case of a 58-year-old woman with a left patellar fracture from a fall. Complete healing was achieved after in 2 months postoperatively using the improved Kirschner wire tension band and a cable grip system; however, at 7 months postoperatively, a prepatellar skin mass appeared. The patient reported prepatellar discomfort with no pain and influence of movement of the knee and daily life. One year postoperatively, we surgically removed the implants and mass. The pathological result showed bursa mucosa. Results: The literature review shows that pain, secondary knee dysfunction, fracture nonunion, and malunion are postoperative complications of patellar fractures. However, prepatellar bursa mucosa have not been previously reported as a postoperative complication. Conclusion: This case highlights the need for appropriate placement of the intraoperative implant in adults with patellar fractures.

BACKGROUND:Nonunion is a major concern for orthopedic surgeons, particularly nonunion of the clavicle, which can cause severe pain, loss of full range of motion, poor sleep quality, and loss of strength in the affected individuals. Platelet-rich plasma (PRP), an important biological agent, is widely used in orthopedics.OBJECTIVE:We used a combination of three techniques - the PRP technique, autologous bone grafting technique, and internal plate fixation technique - to ensure adequate internal fixation and enable a bone growth-supportive environment at the fracture site.METHODS:The surgical approach was applied to a patient with clavicle nonunion.RESULTS:Based on postoperative follow-up findings and intraoperative findings at the time of re-removal of the patient's implant, the prognosis at the fracture site was considered satisfactory.CONCLUSION:We observed that the patient treated with this method had favorable clinical outcomes, and we recommend that this technique be used in patients with long-bone nonunion.

Background:The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects. Methods and results:To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors' results showed that 400 SW pulses at 0.21 mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7. Conclusions:For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.

BACKGROUND:Although tibial shaft fractures are the third most common long bone fractures in children after the forearm and femur, nonunion of these fractures are rare in the pediatric population.CASE REPORT:Despite seldom seen, tibial nonunion is very complex and it is also a devastating complication of tibial fracture especially when infected. Numerous methods have been employed to treat pediatric tibial nonunion, but there is no consensus. Here, we present a case of a child with right tibial shaft fracture nonunion. We treated this patient with ipsilateral free non-vascularized fibular graft.RESULTS:Both the nonunion site and fibular donor site united well with good function in the injured extremity and no adverse events.CONCLUSION:We recommend the use of ipsilateral free non-vascularized fibular graft for the treatment of pediatric tibial shaft nonunion.

The goal of this study was to develop an imaging probe-IRDye-680RD-OX40 mAb-that can be used for noninvasive imaging and optical imaging of rheumatoid arthritis (RA). OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T cell activation. Detectable change in T cell activation profiles was observed in early RA.OX40 expression pattern was analyzed by flow cytometry. N-hydroxysuccinimide (NHS) esters are used to label proteins selectively on free amino groups of OX40 monoclonal antibody (mAb). Characterization of IRDye-680RD-OX40 mAb was measured and a fluorescence spectrum gathered. Cell binding assay was also performed between activated and naïve murine T cells. Longitudinal near-infrared fluorescence (NIRF) imaging of the probe was performed on day 8, day 9, day 10, and day 11 of adjuvant-induced arthritis (AIA) mouse model. Paw thickness and body weight were compared between the OX40 mAb and IgG injection groups.NIRF imaging with IRDye-680RD-OX40 mAb revealed strong OX40-positive responses with high specificity. Flow analysis showed that OX40 was specifically expressed on the surface of T cells in RP and spleen of AIA model. The AIA group was significantly differentiated from the control group at all time points with imaging monitoring. The region of interest (ROI) was in line with ex vivo imaging and biodistribution study. This study highlights the potential utility of the OX40 NIRF imaging as a new strategy for RA prediction and T cell monitoring.The results provide evidence that IRDye-680RD-OX40 mAb detects organized T cells activation in early RA. The optical probe was capable of detection of RA pathogenesis. It identified transcriptional responses to RA that mediate its immune functions. Thus, it may be an ideal probe for RA imaging.

Objective:To investigate the clinical efficacy of robot-assisted minimally invasive sacroiliac screw fixation combined with LC-II external fixation in the treatment of pelvic fracture.Methods:A retrospective analysis was conducted on 28 cases with pelvic fractures treated with robot-assisted minimally invasive sacroiliac screw fixation combined with LC-II external fixation from May 2018 to November 2022. There were 19 males and 9 females, with an average age of 43.4±16.9 years (range, 14-74 years). There was 1 case of B1 type, 1 case of B2 type, 4 cases of B3 type, 10 cases of C1 type, 9 cases of C2 type and 3 cases of C3 type by Tile classification. All the cases were treated with closed reduction, LC-II external fixation for the anterior lesions and robot-assisted minimally invasive sacroiliac screw fixation for the posterior lesions. The operation time, fluoroscopy time and excellent rate of screw placement were recorded. The quality of fracture reduction was evaluated by Matta's criteria, and the clinical effect was evaluated by Majeed score.Results:All the 28 cases successfully underwent the surgery. In 11 cases the fractures were reduced by the pelvic unlocking closed reduction device while in the other 17 cases manual reduction was applied. In this cohort, 43 screws were implanted. All the screw positions reached level I by Gras grading. The average fluoroscopy time was 16.3±5.2 s (range, 9-31 s) per screw. The average operation time was 154.9±54.7 min (range, 55-226 min). According to the Matta's criteria, the reduction was rated as excellent in 19 cases, good in 7 cases, fair in 2 cases, yielding an excellent or good rate of 93% (26/28). No iatrogenic neurovascular injury was found in all the 28 patients. The average follow-up was 18.3±7.3 months (range, 4-31 months). The fractures healed at 3.6±1.1 months (range, 2-6 months) after the surgeries. At the final follow-up, the results of the Majeed scores were rated as excellent in 13 cases, good in 11 cases, fair in 3 cases and poor in 1 case, with an excellent or good rate of 86% (24/28).Conclusion:The technique of robot-assisted minimally invasive sacroiliac screw fixation combined with LC-II external fixation used in the treatment of pelvic fracture showed good clinical results.

高能量损伤是股骨干骨折最常见的原因,股动脉损伤是股骨干骨折的一种少见合并伤.0. 1％～2％的股骨干骨折合并股动脉损伤,一旦发生,失血迅速,若诊断治疗不正确、及时,可危及生命[1].因此早期诊断和治疗至关重要.本文报告了1例股骨干开放性骨折合并股动脉断裂的病例,以期提高对股动脉损伤这一股骨干骨折少见合并伤的认识,并为临床相关病例救治提供参考.

Objective:To investigate the clinical efficacy of TiRobot-assisted minimally invasive percutaneous screw fixation for pelvic fractures.Methods:The clinical data of 44 patients with pelvic fracture were retrospectively analyzed who had undergone TiRobot-assisted minimally invasive percutaneous screw fixation from May 2018 to April 2021 at Department of Orthopedic Traumatology, The First Hospital of Jilin University. There were 30 males and 14 females, aged from 11 to 78 years (average, 40.6 years). According to the Tile classification, there were 20 type C1 fractures, 23 type C2 fractures and one type C3 fracture. The time from injury to operation averaged 8.2 days (from 1 to 41 days). The minimally invasive percutaneous screw fixation was assisted by the orthopaedic TiRobot in all patients. Operation time, fluoroscopy time, reduction quality, complications and functional recovery at the final follow-up were recorded and analyzed.Results:A total of 96 screws were implanted in this cohort. The total fluoroscopy time ranged from 17 to 66 s, with an average of 17.8 s for each single screw. The operation time ranged from 50 to 355 min, averaging 179.7 min. According to the Matta criteria, the reduction quality was rated as excellent in 36 cases, as good in 5 and as fair in 3, yielding an excellent and good rate of 93.2%(41/44). All the 44 patients were followed up for 6 to 42 months (average, 20.4 months). The fracture healing time ranged from 2 to 6 months, averaging 3.3 months. The Majeed scores at the final follow-up ranged from 51 to 100 points (average, 83.7 points); there were 28 excellent, 8 good, 7 fair and one poor cases, giving an excellent to good rate of 81.8% (36/44). Follow-up found no such complications as iatrogenic neurovascular injury, incision infection, malunion, implant loosening or fracture re-displacement in all the 44 patients.Conclusion:TiRobot-assisted minimally invasive internal fixation can result in fine clinical efficacy for pelvic fractures, showing advantages of accuracy, minimal invasion and safety.

OBJECTIVE To study swimming exercise's effect on caspase-3 expression in chondrocytes in osteoarthritis (OA). METHODS 36 SD rats were randomly separated into normal group (n = 12), OA model group (n = 12) and swimming exercise group (n = 12). After modeling, rats received no intervention in model group and swimming exercise once a day (15 min/time) for 4 consecutive weeks in swimming exercise group. After intervention for 4 weeks, specimens were taken to analyze tissue morphology by H&E staining, caspase-3 expression by Western blot and qPCR, chondrocytes apoptosis by TUNEL assay. RESULTS HE staining revealed abnormal bone tissue morphology in model group and swimming exercise group with improved morphology after swimming exercise. Model group and swimming exercise group all showed significantly higher Caspase-3 protein level than normal group with lower level after swimming exercise (P < 0.05). Consistently, qPCR showed similar expression profile of caspase-3 mRNA level to the protein level. CONCLUSION Swimming exercise can inhibit caspase-3 level and chondrocytes apoptosis in OA, thus improving the joint morphology.

Introduction: The efficacy of the most commonly used interventions for clavicle fractures remains controversial. These interventions are: open reduction and plate fixation (ORPF), non-surgical intervention (NSI), and use of an intramedullary nail (IMN). In adult patients with clavicle fractures, choosing which intervention might be best is challenging. Materials and methods: PubMed, Journals@Ovid Full Text, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and Embase were performed to search English-language studies from the inception to February 2020. Randomized controlled trials (RCTs) comparing any of these three interventions were included. Patient and baseline characteristics, nonunion, major complications, Constant-Murley score (CMS), and Disabilities of the Arm, Shoulder and Hand score (DASH) were extracted. Then, we evaluated the functional outcomes and adverse effects after use of these three interventions for the management of displaced midshaft clavicle fractures in a Bayesian network meta analysis. Results: A Bayesian random-effects model was conducted, and nonunion and major complications were evaluated with: risk ratio (RR) and 95% confidential interval (CI); while CMS and DASH were evaluated with mean differences (MD) and the corresponding 95% confidential interval CI. The rank probability of each endpoint was assessed on the basis of the surface area under the cumulative ranking curve (SUCRA). Discussion: ORPF is most likely to be successful in achieving objective functional outcomes as captured by the CMS, and IMN demonstrates significant efficacy for subjective functional outcomes, as captured by DASH scores. Compared with the other interventions examined, IMN was associated with decreased risk for adverse effects. Levels of evidence: I; meta-analysis. (c) 2021 Elsevier Masson SAS. All rights reserved.

The efficacy of the most commonly used interventions for clavicle fractures remains controversial. These interventions are: open reduction and plate fixation (ORPF), non-surgical intervention (NSI), and use of an intramedullary nail (IMN). In adult patients with clavicle fractures, choosing which intervention might be best is challenging. PubMed, [email protected] Full Text, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and Embase were performed to search English-language studies from the inception to February 2020. Randomized controlled trials (RCTs) comparing any of these three interventions were included. Patient and baseline characteristics, nonunion, major complications, Constant-Murley score (CMS), and Disabilities of the Arm, Shoulder and Hand score (DASH) were extracted. Then, we evaluated the functional outcomes and adverse effects after use of these three interventions for the management of displaced midshaft clavicle fractures in a Bayesian network meta-analysis. A Bayesian random-effects model was conducted, and nonunion and major complications were evaluated with: risk ratio (RR) and 95% confidential interval (CI); while CMS and DASH were evaluated with mean differences (MD) and the corresponding 95% confidential interval CI. The rank probability of each endpoint was assessed on the basis of the surface area under the cumulative ranking curve (SUCRA). ORPF is most likely to be successful in achieving objective functional outcomes as captured by the CMS, and IMN demonstrates significant efficacy for subjective functional outcomes, as captured by DASH scores. Compared with the other interventions examined, IMN was associated with decreased risk for adverse effects. I; meta-analysis.

Background: The purpose of this meta-analysis was to comprehensively collect randomized controlled trials (RCTs) to assess the clinical efficacy of intrathecal morphine (ITM) versus local infiltration analgesia (LIA) in the treatment of total knee and hip arthroplasty patients. Methods: Relevant studies were identified from the Embase, PubMed, Cochrane Library, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases. We also reviewed the references of all identified articles to identify additional studies. For each study, we assessed the risk ratio (RR), weighted mean difference (WMD), and corresponding 95% confidence interval (95% CI) to synthesize outcomes. Meta-analysis was performed with Stata 12.0 software. Results: We included 13 studies with 942 patients for meta-analysis. LIA significantly decreased the pain value with rest or mobilization until 72 hours (P < .05). LIA significantly decreased cumulative morphine consumption by 13.52 mg. Moreover, the length of hospital stay was lower in the LIA group than in the ITM analgesia group. Finally, LIA significantly reduced morphine-related complications (nausea and vomiting, pruritus, and respiration depression). Conclusions: LIA was an effective approach for relieving postoperative pain and reducing postoperative consumption of morphine compared with ITM in total knee and hip arthroplasty patients.

A number of meta-analyses have compared clinical outcomes following plate vs. intramedullary fixation for midshaft clavicle fractures (MSCF), but with conflicting results. There is a requirement for updated level-1 evidence to guide clinicians managing MSCF. The aim of the present systematic review and meta-analysis was to compare clinical outcomes following plate vs. intramedullary fixation of MSCF. The PubMed, Scopus, BioMed Central, Cochrane Central Register of Controlled Trials and Google Scholar databases were searched for records added until 1st July 2019. A total of 10 randomised controlled trials (RCTs) were included. Shoulder function was assessed using the Constant-Murley Shoulder Outcome questionnaire and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). There was no statistically significant difference in Constant-Murley scores between plate and intramedullary fixation [Mean difference (MD)=0.75; 95% CI: -2.49 to 3.99; P=0.65; I2=85%]. Similarly, there was no statistically significant difference in DASH scores between the two groups (MD=1.55; 95% CI: -1.12 to 4.23; P=0.26; I2=89%). There was no statistically significant difference in complications requiring non-routine surgery between plate and intramedullary fixation [risk ratio (RR)=1.80, 95%CI: 0.80-4.05, P=0.15; I2=0%]. There was an increased risk of complications that did not require non-routine surgery with plate fixation as compared to intramedullary fixation (RR=2.38, 95%CI: 1.22-4.62, P=0.01; I2=70%). Plate fixation was also associated with an increased risk of infection and complications of cosmetic dissatisfaction. The present results indicated no difference in long-term functional outcomes between plate and intramedullary fixation of MSCF. Plate fixation was associated with an increased risk of complications not requiring non-routine surgery. Further high-quality RCTs shall strengthen the evidence on this subject.

Objective: This study aimed to investigate the clinical efficacy of zoledronic acid combined with percutaneous kyphoplasty (PKP) in the treatment of Osteoporotic vertebral compression fractures (OVCF) via the evaluation of serum metabolic index. Methods: A total of 102 patients with osteoporotic vertebral body compression fractures who were hospitalized in the First Hospital of Jilin University from May 2016 to February 2018 was randomly divided into a control group (group A, n=48) and an experimental group (Group B, n=54). All patients were treated with PKP, and group B was additionally treated with zoledronic acid postoperatively. The pain visual analogue scale (VAS), vertebral bone mineral density (BMD), fracture vertebral height, Cobb angle change, recurrent fracture rate, adverse effects, the incidence of the reaction, tartrate acid phosphonate (TRACP) 5b and type I collagen C-terminal peptide (CTX) levels were tested before operation and 1, 3, 6 and 12 months after operation. Results: No significant difference was found in gender, age, body mass index, postoperative leakage, and traumatic vertebrae between the two groups (P>0.05). BMD, height ratio of injured vertebral body in both groups were increased while VAS score, Cobb angle changes, serum (TRACP) 5b and CTX levels were reduced after the operation compared to those before operation. At 3, 6 and 12 months after operation, the VAS score, Cobb angle changes, the incidence of recurrent fractures, serum (TRACP) 5b and CTX levels in group B was significantly decreased, while the BMD level, vertebral body height ratio, the incidence of adverse reactions in group B was statistically elevated compared to those in group A (P<0.05). Conclusion: Zoledronic acid can significantly increase the clinical efficacy after PKP, which provides leads for the future anti-OVCF therapy.

Abstract Rationale: Floating ankle is a rare traumatic condition characterized by a combination of tibial and ipsilateral foot fractures, with the ankle remaining intact. It is usually caused by high-energy trauma and also presents with serious soft tissue damage. Its treatment is mainly restricted to external fixation, which results in poor outcomes. We present a patient with a floating ankle who underwent staged treatment and achieved full internal fixation, subsequently returning to normal activity. Patient concerns: A 26 year- old man had an accident with an reel machine and sustained an open fracture on his right lower extremity. Diagnoses: Digital radiograph demonstrated a distal tibial fracture, fibular fracture, and multiple metatarsal fractures, which fulfilled the criteria for a floating ankle. Interventions: Initial ankle-spanning external fixation was performed. After 21 days, the patient underwent open reduction and internal fixation on his first and fifth metatarsals, and K-wire fixation on his fourth metatarsal. The external fixator was replaced by plaster fixation. Seven days later, the patient underwent internal fixation of his leg, open reduction and internal fixation with plating was applied of the fibular fracture, and minimally invasive plate osteosynthesis of the tibial fracture. Outcomes: At 1-year follow-up, bone union was identified by digital radiograph; after 2 years, his ankle function had fully recovered, and he resumed his normal activities. Lessons: In the staged treatment protocol of the floating ankle, temporary external fixation provided traction and immobilization of the skeletal and soft tissues. Secondary internal fixation maintained the reduction and alignment and allowed early exercise, which is critical to the prognosis of a floating ankle.

Calcium dysregulation is a key pathological event in Alzheimer’s disease (AD). In studying approaches to mitigate this calcium overload, we identified the collapsin response mediator protein 2 (CRMP2), an axonal guidance protein that participates in synapse dynamics by interacting with and regulating activity of N-methyl-D-aspartate receptors (NMDARs). We further identified a 15 amino acid peptide from CRMP2 (designated CBD3, for calcium-binding domain 3), that reduced NMDAR-mediated Ca 2+ influx in cultured neurons and post-synaptic NMDAR-mediated currents in cortical slices. Whether targeting CRMP2 could be therapeutically beneficial in AD is unknown. Here, using CBD3, we tested the utility of this approach. Employing the APP/PS1 mouse model of AD which demonstrates robust pathophysiology including Aβ1–42 deposition, altered tau levels, and diminished cognitive functions, we asked if overexpression of CBD3 could rescue these events. CBD3 was engineered into an adeno-associated vector and nasally delivered into APP/PS1 mice and then biochemical (immunohistochemistry, immunoblotting), cellular (TUNEL apoptosis assays), and behavioral (Morris water maze test) assessments were performed. APP/PS1 mice administered adeno-associated virus (AAV, serotype 2) harboring CBD3 demonstrated: (i) reduced levels of Aβ1–42 and phosphorylated-tau (a marker of AD progression), (ii) reduced apoptosis in the hippocampus, and (iii) reduced cognitive decline compared with APP/PS1 mice or APP/PS1 administered a control virus. These results provide an instructive example of utilizing a peptide-based approach to unravel protein-protein interactions that are necessary for AD pathology and demonstrate the therapeutic potential of CRMP2 as a novel protein player in AD.