Noninterportal capsulotomy of hip arthroscopy showed improved outcomes in borderline hip dysplasia: A retrospective study with minimum 2-year follow-up.

PURPOSE: The present study aimed to evaluate the functional outcomes of hip arthroscopy using a noninterportal capsulotomy technique to address labral tears in patients with borderline hip dysplasia (BHD). Additionally, we also compared these outcomes with those of patients with BHD who underwent the standard repaired interportal capsulotomy (RIPC) arthroscopy. METHODS: Data from patients with BHD were retrieved from a database of patients who underwent arthroscopic hip surgery with noninterportal capsulotomy or RIPC to treat labral tears between January 2014 and December 2020. Data collected included both pre- and postoperative patient-reported outcomes (PROs). RESULTS: A total of 58 patients (noninterportal capsulotomy, n = 37; RIPC, n = 21) with a mean age of 30.9 ± 5.6 and 28.6 ± 5.5 years, respectively, met the inclusion criteria. All of the patients underwent a minimal 2-year follow-up. The mean lateral centre-edge angle was 23.3 ± 1.2° in the noninterportal capsulotomy group and 23.7 ± 1.0° in the RIPC group, with no significant difference. The PROs improved from the preoperative to the latest follow-up, with a p < 0.001. There were no differences between the groups. CONCLUSION: Using strict patient selection criteria, hip arthroscopy with noninterportal capsulotomy demonstrated significant pre- to postoperative improvements in patients with BHD and achieved results comparable to those from hip arthroscopy with RIPC. LEVEL OF EVIDENCE: Level III.

Exosomes as Targeted Delivery Platform of CRISPR/Cas9 for Therapeutic Genome Editing.

Therapeutic genome editing harnesses the power of genome editing tools to correct erroneous genes associated with disease pathology. To bring the CRISPR/Cas9 tool from the bench to the bedside, a critical hurdle is the safe and efficient delivery of this nucleic acid tool to the desired type of cells in patients. This review discusses the use of natural carriers, extracellular vesicles (EVs), in particular exosomes, to fill the gap. Exosomes are lipid-containing nanovesicle released by various types of cells to mediate cell-cell communications. Their inherent long-distance transportation capability, biocompatibility, and engineerability have made EVs potential vehicles for delivering therapeutic drugs. We summarize the recent progress of harnessing exosomes as delivery vehicles for the CRISPR/Cas system to achieve therapeutic gene editing for disease treatment, with a focus on various strategies to achieve selective delivery to a particular type of cell and efficient packaging of the genome editing tools in the vesicles. Critical issues and possible solutions in the design and engineering of the targeting vehicles are highlighted. Taken together, we demonstrate EV/exosome-mediated packaging of the nucleic acid/protein tools and the cell/tissue-targeted delivery to be a viable way towards the clinical translation of the CRISPR/Cas9 technology.

Arthroscopic repair of the medium-size rotator cuff tear with the novel technique of the point union bridge: a minimum 2-year follow-up cohort study.

BACKGROUND: Achieving secure fixation and preventing retear have been recognized as fundamental in arthroscopic repair of rotator cuff tears. Moreover, reducing internal implantation can lower medical expenses and minimize the operation time, which is essential for the surgical safety and postoperative rehabilitation of the patients. We have recently proposed the point union bridge (PUB) suture configuration as a novel method for not only providing equivalent fixation but also decreasing the operation time and medical expenses. However, no comparative clinical studies have been performed. METHODS: From March 2014 to September 2016, a total of 88 patients with diagnoses of medium-size rotator cuff tears underwent arthroscopic repair with a randomly assigned technique-either the PUB technique (n = 42) or the double-row suture bridge (DRSB) technique (n = 46). All patients underwent a minimal 2-year follow-up. We used the Constant-Murley score (CMS), American Shoulder and Elbow Surgeons (ASES) score, active and passive range of motion, and visual pain-simulation score (visual analog scale [VAS] score) to assess the functional outcomes. In addition, we recorded the arthroscopic operation time, medical costs, and postoperative complications. All patients received magnetic resonance imaging at the 6-month and 2-year postoperative evaluations to assess structural integrity and tendon healing. RESULTS: At the 2-year follow-up, all scoring parameters evaluated (CMS, ASES score, and VAS score), as well as active and passive range of motion, improved significantly in both groups as compared with preoperative assessments. The PUB technique significantly decreased the operation time (55.9 ± 14.1 minutes vs. 72.2 ± 14.2 minutes for PUB vs. DRSB, P < .001) and medical expenses ($2608.0 ± $391.1 vs. $4056.9 ± $350.9 for PUB vs. DRSB, P < .001). However, no significant differences between the 2 techniques were found in any functional assessments of the shoulder (CMS, ASES score, and VAS score), repair integrity, or the retear rate at the 2-year follow-up. CONCLUSION: Arthroscopic repair of the medium-size rotator cuff tear with either the PUB or DRSB technique could yield both satisfactory improvements in the shoulder function of patients and equivalent tendon integrity. With less consumption of internal implants, the PUB technique significantly reduced the operation time and decreased medical expenses.

The imaging evaluation of acetabular labral lesions.

The acetabular labrum is an important structure that contributes to hip joint stability and function. Diagnosing labral tears involves a comprehensive assessment of clinical symptoms, physical examinations, imaging examinations, and arthroscopic confirmation. As arthroscopy is an invasive surgery, adjuvant imaging of the acetabular labrum is increasingly imperative for orthopedists to diagnose and assess labral lesions prior to hip arthroscopy for surgical management. This article reviews the current imaging strategies for the evaluation of labrum lesions.

Clinical outcomes and radiologic assessment of a modified suture button arthroscopic Latarjet procedure.

BACKGROUND: As several neurologic and hardware complications have been reported with screw fixation. Suture buttons are used to serve as an alternative to screw fixation to obtain better outcome and to reduce the complication. The purpose of this study was to observe the clinical outcomes and make the radiologic assessment of a modified suture button (MSB) arthroscopic Latarjet procedure. METHODS: A total of ninty-one patients with recurrent shoulder joint dislocation who underwent MSB arthroscopic Latarjet procedure was retrospectively reviewed. Fifty cases identified from the chart review met the inclusion criteria. The clinical outcomes and position of the grafts, glenohumeral degeneration, and graft healing condition were assessed postoperatively in a follow-up with at least one and half of a year. RESULTS: All the fifty patients were satisfied with their clinical outcome. The overall complication rate was 4% in this study. The mean visual analog scale score, the affected shoulder active mobility in Ers(external rotation at the side), Era(external rotation in abduction) decreased significantly; the ASES score, Rowe score, Walch-Duplay score improved significantly. CT scans in the sagittal view showed that grafts in 88% of cases were in good position, grafts in 12% of cases were fixed too superiorly and inferiorly. In the axial view grafts in forty cases were flush with the glenoid rim, ten were considered as too lateral. The ten grafts became remodeled and were more flush with the glenoid rim in the follow-up. CONCLUSIONS: The MSB arthroscopic Latarjet procedure provides excellent outcome with few complications, and no degenerative changes were observed in the follow-up. Moreover, the graft fixed too laterally presented a phenomenon of remodeling and became flush with the glenoid rim over time.

Repair of articular cartilage defects with intra-articular injection of autologous rabbit synovial fluid-derived mesenchymal stem cells.

BACKGROUND: The role of rabbit synovial fluid-derived mesenchymal stem cells (rbSF-MSCs) in cartilage defect repair remains undefined. This work evaluates the in vivo effects of rbSF-MSCs to repair knee articular cartilage defects in a rabbit model. METHODS: Cartilage defects were made in the patellar grooves of New Zealand white rabbits. The rbSF-MSCs were generated from the knee cavity by arthrocentesis. Passage 5 rbSF-MSCs were assayed by flow cytometry. The multipotency of rbSF-MSCs was confirmed after 3 weeks induction in vitro and the autologous rbSF-MSCs and predifferentiated rbSF-MSCs were injected into the synovial cavity. The intra-articular injection was performed once a week for 4 weeks. The animals were euthanized and the articular surfaces were subjected to macroscopic and histological evaluations at 8 and 12 weeks after the first intra-articular injection. RESULTS: Hyaline-like cartilage was detected in the defects treated with rbSF-MSCs, while fibrocartilage tissue formed in the defects treated with chondrocytes induced from rbSF-MSCs. CONCLUSIONS: Our results suggest that autologous undifferentiated rbSF-MSCs are favorable to articular cartilage regeneration in treating cartilage defects.

A retrospective comparative study of arthroscopic fixation in acute Rockwood type IV acromioclavicular joint dislocation: single versus double paired Endobutton technique.

BACKGROUND: Rockwood type IV acromioclavicular joint (ACJ) dislocation is a trauma usually needs surgical treatment. Paired EndoButton technique (PET) is used in treating such condition. However, the effect of using different types of PET (single versus double PET) for fixation remains controversial. This study aims to evaluate and compare the efficacy of single and double PET and to provide a suitable option for the surgeons. METHODS: We retrospectively reviewed the charts of patients with acute Rockwood type IV ACJ dislocation who had undergone arthroscopic fixation using single or double PET fixation between March 2009 and March 2015. Seventy-eight consecutive patients identified from chart review were picked and were divided into the single and double PET group with 39 cases in each group. The indexes of visual analog scale score (VAS) for pain, the radiographs of the affected shoulder at different time points of the follow-up, the time of return to activities and sports, the constant functional score, and the Karlsson acromioclavicular joint (ACJ) score, were assessed in a minimum of 2 years postoperation. RESULTS: The average coracoclavicular (CC) and acromioclavicular (AC) distances of the affected joints in the double PET group were significantly smaller than those of the single PET group 2 years postoperation (P < 0.05). The average AC and CC distances in the healthy shoulder joints were significantly smaller than those of the affected joints in the single PET group (P < 0.05); however, these values were not significantly different from those of the affected joints in the double PET group (P > 0.05). The mean VAS pain score was not significantly different, while significant difference was found for the number and times of cases return to activities and sports, constant functional score, and Karlsson ACJ score (P < 0.05) between the two groups. Therefore, the double PET group has better outcome than the single PET group. Complications including redislocation, button slippage, erosion, or AC joint instability occurred in the single PET group, while the complication in the double PET group was rare. CONCLUSIONS: Compared with the single PET, the double PET group achieved better outcome with less complications in arthroscopically treating acute Rockwood type IV ACJ dislocation.

Comparison of Extraosseous Talotarsal Stabilization Implants in a Stage II Adult-Acquired Flatfoot Model: A Finite Element Analysis.

Subtalar arthroereisis has been proved to be an efficient method for correcting flexible adult flatfoot. However, the optimal sinus tarsi implant is still debated and yet to be determined. In the present study, we compared the biomechanical effects of type I and II sinus tarsi implants in stage II adult-acquired flatfoot deformity (AAFD). First, a finite element model of stage II AAFD was established in which virtual surgery of subtalar arthroereisis was simulated. The indexes of plantar stress distribution, peak von Mises of the medial and lateral columns, strain of the medial ligaments and plantar fascia, arch height, talo-first metatarsal angle, calcaneus pitch angle, talonavicular coverage angle, and hindfoot valgus angle were all compared and analyzed. The results of the present study have validated the stage II AAFD finite element model by comparing the simulation results with the same parameters measured from weightbearing radiographs in the midstance phase. All the indexes showed that both types of arthroereisis can lower the plantar pressure and the strain of the medial ligaments that support the medial longitudinal arch and can shift the load of the medial column to the lateral column. They can also help to correct the deformity and restore the arch. However, the type II sinus tarsi implant design exhibited a more obvious effect than that of type I.

[Mid-term effectiveness of LU-tarjet procedure for recurrent anterior shoulder dislocation].

Objective: To evaluate the mid-term effectiveness of limited unique coracoid osteotomy suture button fixation Latarjet (LU-tarjet) procedure in treatment of recurrent anterior shoulder dislocation. Methods: Between March 2017 and February 2019, 56 patients with recurrent shoulder dislocation were treated with arthroscopic LU-tarjet procedure. There were 44 males and 12 females with an average age of 26.3 years (range, 18-41 years). Shoulder joint dislocation occurred 2-16 times, with an average of 7.5 times. The time from the initial dislocation to operation ranged from 6 months to 13 years, with a median of 4.6 years. Preoperative shoulder joint fear test and re-reduction test were positive in all patients. The Beighton score of joint relaxation ranged from 1 to 7, with an average of 4.1. The shoulder Instability Severity Index Score (ISIS) ranged from 5 to 10, with an average of 7.8. The size of glenoid defects on the affected side ranged from 15% to 32% (mean, 22.4%). All patients had Hill-Sachs injuries of varying degrees. Six patients had re-dislocation after Bankart surgery. The operation time, incision healing, and postoperative complications were recorded. The range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation) of shoulder joint were compared between pre- and post-operation. The improvement of shoulder function was evaluated using the American Association for Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, and Rowe score. X-ray films and three-dimensional CT were used to analyze the location, healing, and remolding of bone graft, the repair of glenoid defect, and degenerative changes of the shoulder joint. Results: All operations were successfully completed. The operation time ranged from 42 to 98 minutes, with an average of 63 minutes. All incisions healed by first intention. All patients were followed up 5-7 years (mean, 6.3 years). During follow-up, 2 patients experienced shoulder subluxation within 1 year after operation and 1 patient experienced recurrent shoulder joint pain. The remaining patients had no related complications. At last follow-up, there was no significant difference between the two groups ( P>0.05) in range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation). The ASES score, Rowe score, and Walch-Duplay score of shoulder significantly improved when compared with those before operation ( P<0.05). Postoperative CT showed that 53 cases (94.64%) of coracoid bone masses were centered placed vertically, 2 cases (3.57%) were superior, and 1 case (1.79%) was inferior; 49 cases (87.50%) of the coracoid bone grafts were flush with the glenoid, 2 cases (3.57%) and 5 cases (8.93%) were medially and laterally positioned. The volume of coracoid bone graft decreased first and then increased, and the shape of the bone graft was continuously remodeling and gradually matched with the track of the humerus head (the optimal circle of the glenoid), all coracoid bone grafts healed. At last follow-up, the coverage rate of optimal glenoid circle was 89.6%-100%, with an average of 97.4%. The area of glenoid defect was 2.6%±1.3%, which significantly decreased when compared with preoperative (22.4%±5.4%) ( P<0.05). At last follow-up, no obvious degenerative changes of shoulder joint was observed. Conclusion: LU-tarjet procedure for recurrent anterior shoulder dislocation has good mid-term effectiveness with short operation time and few complications.

Osteoclast-targeted delivery of anti-miRNA oligonucleotides by red blood cell extracellular vesicles.

Osteoporosis (OP) affects millions worldwide but currently cannot be cured. Suppressing the level of miR-214 in osteoclasts by the anti-miRNA oligonucleotide (AMO) anti-miR-214 reverses bone absorption and provides a potential treatment. Here we report a peptide-guided delivery strategy using red blood cell extracellular vesicles (RBCEVs) as the vehicle to realize osteoclast-targeted delivery of anti-miR-214. A bi-functional peptide, TBP-CP05, which binds to both the CD63 on RBCEVs and receptors on osteoclasts, acts as the guide. TBP-CP05 binds with RBCEVs through CP05, displays the TRAP-binding peptide (TBP) on the surface of EVs, and endows RBCEVs with osteoclast-targeting capability both in vitro and in vivo. Intravenous injection of the osteoclast-targeting RBCEVs (OT-RBCEVs) led to the enrichment of EVs in the bone skeleton, significant inhibition of the osteoclast activity, elevated osteoblast activity, and improved bone density in osteoporotic mice. Altogether, this work demonstrates efficient guidance of drug-loaded EVs to the targeted cells in vivo using bi-functional fusion peptides, and showcases that targeted delivery of anti-miR-214 by OT-RBCEVs may be a viable method for OP treatment. SIGNIFICANCE STATEMENT. Surface functionalization of EVs endows these nanovesicles cell-specific targeting property which guides the drug cargos to specific tissues and cells with higher accuracy, longer retention, and minimal off-target effects. Methods to functionalize EVs with minimal procedures are highly desired for clinical applications. Here we present a facile method using a bifunctional fusion peptide to guide RBCEVs to osteoclasts. A simple incubation of the bifunctional peptide and RBCEVs results in osteoclast-targeting RBCEVs (OT-RBCEVs) that effectively deliver anti-miR-214 to osteoclasts in vivo in a mouse model of osteoporosis, bringing a potential therapy to osteoporotic patients. This is, to our knowledge, the first report on peptide functionalization of RBCEVs and osteoclast-targeted delivery using RBCEVs.

Large-scale Preparation of Synovial Fluid Mesenchymal Stem Cell-Derived Exosomes by 3D Bioreactor Culture.

Exosomes secreted by mesenchymal stem cells (MSCs) have been suggested as promising candidates for cartilage injuries and osteoarthritis treatment. Exosomes for clinical application require large-scale production. To this aim, human synovial fluid MSCs (hSF-MSCs) were grown on microcarrier beads, and then cultured in a dynamic three-dimension (3D) culture system. Through utilizing 3D dynamic culture, this protocol successfully obtained large-scale exosomes from SF-MSC culture supernatants. Exosomes were harvested by ultracentrifugation and verified by a transmission electron microscope, nanoparticle transmission assay, and western blotting. Also, the microbiological safety of exosomes was detected. Results of exosome detection suggest that this approach can produce a large number of good manufacturing practices (GMP)-grade exosomes. These exosomes could be utilized in exosome biology research and clinical osteoarthritis treatment.

Cell-derived extracellular vesicles for CRISPR/Cas9 delivery: engineering strategies for cargo packaging and loading.

Genome editing technology has emerged as a potential therapeutic tool for treating incurable diseases. In particular, the discovery of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems and the design of single-guide RNAs (sgRNAs) have revolutionized genome editing applications. Unfortunately, compared with the rapid development of gene-editing tools, the progress in the development of delivery technologies is lagging behind and thus limiting the clinical application of genome editing. To overcome these limitations, researchers have investigated various delivery systems, including viral and non-viral vectors for delivering CRISPR/Cas and sgRNA complexes. As natural endogenous nanocarriers, extracellular vesicles (EVs) present advantages of biocompatibility, low immunogenicity, stability, and high permeability, making them one of the most promising drug delivery vehicles. This review provides an overview of the fundamental mechanisms of EVs from the aspects of biogenesis, trafficking, cargo delivery, and function as nanotherapeutic agents. We also summarize the latest trends in EV-based CRISPR/Cas delivery systems and discuss the prospects for future development. In particular, we put our emphasis on the state-of-the-art engineering strategies to realize efficient cargo packaging and loading. Altogether, EVs hold promise in bridging genome editing in the laboratory and clinical applications of gene therapies by providing a safe, effective, and targeted delivery vehicle.

Chondrocyte-specific genomic editing enabled by hybrid exosomes for osteoarthritis treatment.

Rationale: A cell-specific delivery vehicle is required to achieve gene editing of the disease-associated cells, so the hereditable genome editing reactions are confined within these cells without affecting healthy cells. A hybrid exosome-based nano-sized delivery vehicle derived by fusion of engineered exosomes and liposomes will be able to encapsulate and deliver CRISPR/Cas9 plasmids selectively to chondrocytes embedded in articular cartilage and attenuate the condition of cartilage damage. Methods: Chondrocyte-targeting exosomes (CAP-Exo) were constructed by genetically fusing a chondrocyte affinity peptide (CAP) at the N-terminus of the exosomal surface protein Lamp2b. Membrane fusion of the CAP-Exo with liposomes formed hybrid CAP-exosomes (hybrid CAP-Exo) which were used to encapsulate CRISPR/Cas9 plasmids. By intra-articular (IA) administration, hybrid CAP-Exo/Cas9 sgMMP-13 entered the chondrocytes of rats with cartilage damages that mimicked the condition of osteoarthritis. Results: The hybrid CAP-Exo entered the deep region of the cartilage matrix in arthritic rats on IA administration, delivered the plasmid Cas9 sgMMP-13 to chondrocytes, knocked down the matrix metalloproteinase 13 (MMP-13), efficiently ablated the expression of MMP-13 in chondrocytes, and attenuated the hydrolytic degradation of the extracellular matrix proteins in the cartilage. Conclusion: Chondrocyte-specific knockdown of MMP-13 mitigates or prevents cartilage degradation in arthritic rats, showing that hybrid CAP-Exo/Cas9 sgMMP-13 may alleviate osteoarthritis.

Too proactive to switch off: When taking charge drains resources and impairs detachment.

Although proactive behavior is an important determinant of individual work performance, its consequences for employee well-being and other personal outcomes have been largely neglected. In this study, we adopted a within-person perspective to investigate how taking charge behavior (a form of proactivity) affects employees' life outside of work by examining when and how it impacts on their ability to detach and recover from work. Drawing upon resource drain theory, we hypothesized that taking charge has the potential to undermine the process of detachment and recovery from work by draining personal resources. However, based on self-determination theory, we identified autonomous motivation as an essential boundary condition, such that the negative effects of taking charge on detachment and recovery via resource drain occur only when daily autonomous motivation is low. We tested this model on a sample of 77 managers, who provided daily survey data 3 times per day over 5 consecutive working days. Our analyses showed that daily taking charge behavior was negatively related to detachment in the evening, via resource drain, only on days in which people reported low autonomous motivation at work. However, this conditional effect of taking charge did not reach through to next morning recovery. No negative effects of daily taking charge on detachment were observed when people had high autonomous motivation. Overall, these findings suggest that, under some motivational conditions, proactivity can consume resources and interfere with the process of detachment. We offer practical advice for how organizations might encourage proactive behavior while minimizing its drawbacks. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Arthroscopic Treatment of Acetabular Rim Fracture after Traumatic Posterior Hip Dislocation: A Case Series Study.

OBJECTIVE: To investigate the clinical and radiographic short-term results of arthroscopic treatment for posterior labrum tears with an attached bony fragment after traumatic posterior hip dislocation. METHODS: Between July 2014 and May 2019, a consecutive series of nine patients diagnosed with a posterior labrum tear with an attached bony fragment after traumatic posterior hip dislocation were treated by hip arthroscopic techniques. The patients had been injured in traffic accidents (n = 6) or high falls (n = 3). All patients were provided primary treatment at the emergency department of our institution, and then were transferred to our department for arthroscopy. Demographic data (e.g. gender, age, etc), intraoperative findings, the preoperative and postoperative multiple clinical scores and radiological results were subsequently assessed. Visual analogue scale for pain (VAS) and modified Harris hip scores (mHHSs) were measured and compared before surgery, and at the last follow-up. RESULTS: A total of nine patients were enrolled, all of them were male, with a mean age at surgery of 32.2 ± 5.6 years (range, 22-65 years). The patients were followed-up for an average of 26.5 ± 4.1 (range, 24 to 50 years). During the arthroscopic surgery, all patients had labral tears with posterior acetabular rim fracture. All patients had loose osteochondral fragments. Five had partial or complete tears of ligamentum teres. Two patients had osteochondral damage. Two had capsular rupture. Postoperative X-ray films and three dimension computed tomography (3D-CT) showed satisfactory reduction of posterior acetabular wall fractures. The mHHS before surgery and at 1 year and 2 years after surgery were 51.8 ± 4.3, 81.8 ± 2.0 and 87.5 ± 1.9 respectively; VAS scores were 5.6 ± 0.5, 1.3 ± 0.3 and 0.7 ± 0.3 respectively. As compared with the condition before surgery, there was a significant improvement in the mHHS and VAS scores at 1 year and 2 years after surgery (P < 0.01). There was no significant improvement in the mHHS and VAS scores between 1 year and 2 years after surgery (P < 0.05). At the final follow-up, all patients had regained full range of motion (ROM) and were satisfied with the results. None of the patients showed signs of heterotopic ossification, avascular necrosis or progression of osteoarthritis of the hip joint. CONCLUSION: Traumatic dislocation is accompanied by a variety of intra-articular hip joint pathologies. Managing posterior acetabular rim fracture after traumatic posterior hip dislocation using arthroscopic reduction and fixation with anchors is a safe and minimally invasive option and delays the progression of traumatic osteoarthritis.

ERα-Targeting PROTAC as a Chemical Knockdown Tool to Investigate the Estrogen Receptor Function in Rat Menopausal Arthritis.

Proteolytic targeting chimeras (PROTACs) is a rapid and reversible chemical knockout method. Compared with traditional gene-editing tools, it can avoid potential genetic compensation, misunderstandings caused by spontaneous mutations, or gene knockouts that lead to embryonic death. To study the role of estrogen receptor alpha (ERα) in the occurrence and progression of menopausal arthritis, we report a chemical knockout strategy in which stable peptide-based (PROTACs) against ERα to inhibit their function. This chemical knockdown strategy can effectively and quickly inhibit ERα protein in vivo and in vitro. In the rat menopausal arthritis model, this study showed that inhibiting estrogen function by degrading ERα can significantly interfere with cartilage matrix metabolism and cause menopausal arthritis by up-regulating matrix metalloproteinase (MMP-13). The results of this study indicate that ERα is a crucial estrogen receptor for maintaining cartilage metabolism. Inhibition of ERα function by PROTACs can promote the progression of osteoarthritis.

Arthroscopic acetabular labrum reconstruction with capsular autograft: clinical outcome and preliminary results.

To introduce a novel technique to reconstruct the acetabular labrum using capsular autograft, and to evaluate the preliminary clinical outcome, a retrospective review of a prospectively collected registry was undertaken that identified 21 patients (21 hips) who underwent arthroscopic reconstruction of the labrum by capsular autograft from January 2016 to January 2018. Modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), and Hip Outcome Score-Activities of Daily Living (HOS-ADL) were recorded preoperatively and postoperatively. Clinical outcome was analyzed to evaluate the effectiveness of this technique. Twenty-one patients, with an average follow-up time of 25.4 ± 1.6 months, were included in this study: 7 patients were diagnosed with hypoplastic labrum (width <5 mm), 9 patients with complex tear of labrum, and 5 patients with degenerative labrum. The mHHS (61.3 ± 5.5 vs. 87.5 ± 4.2, P<0.001), HOS (52.5 ± 5.1 vs. 87.3 ± 3.8, P<0.001) and HOS-ADL (48.5 ± 5.8% vs. 75.2 ± 3.5%, P<0.001) between preoperative and the 6-month follow-up were significantly different. Gender exerts no influence on the outcome of mHHS, HOS and HOS-ADL. Therefore, local capsular autograft is readily available during arthroscopy with no donor-site morbidity. The reconstruction of the hip labrum may be valuable for patients with hypoplastic or dysplastic labrum, complex tear of labrum and severe degeneration. With appropriate patient selection, this technique is promising in preliminary clinical outcome.