Subchondral Sclerosis Research Articles

Conventional Radiography of Grade III Knee Osteoarthritis: A Case Report

Introduction: Osteoarthritis (OA) is the most common form of inflammatory joint disease. It occurs most frequently in the knees, hips, the spine (vertebrae), and ankles. Radiological prevalence of knee OA in Indonesia reaches 15.5% in men and 12.7% in women aged between 40-60 years. X-ray imaging is routinely used in clinical practice to confirm knee OA diagnosis and in clinical research to monitor the progression of knee OA. Case report: A 62-year-old female patient presented with knee pain in both knees that had been ongoing for the past 6 months. The pain was described as throbbing and stabbing, the right knee worse affected than the left. Palpation elicited tenderness, crepitus in both joints and did not reveal any deformities. Radiological AP/Lateral X-ray of the right knee revealed evidence of osteophytes, sclerosis and narrowing joint space, leading to the impression of Grade III osteoarthritis in the right knee. Discussion: Joint pain is the chief complaint that leads patients with knee osteoarthritis to seek medical attention. Pain typically worsens with movement and decreases with rest. In diagnosing OA, an AP/Lateral radiographic examination of the right knee is conducted, revealing the presence of osteophytes, subchondral bone sclerosis and accompanied by slight joint narrowing. This impression aligns with the Grade III OA criteria according to the Kellgren-Lawrence grading system. Conclusion: Diagnosis of osteoarthritis involves a comprehensive approach combining medical history, physical examination, and diagnostic tests. Radiographic examinations including conventional radiography play a significant role in diagnosing OA. In the early stages of the disease, joint radiographs may still appear normal. The severity of knee OA can be evaluated using the Kellgren-Lawrence (KL) grading scheme which ranges from grade 0 to grade 4. Keywords: Knee Osteoarthritis, Conventional Radiography, The Kellgren-Lawrence Grading

Comparison of 18F-sodium fluoride positron emission tomography and computed tomography for imaging of the fetlock in 25 nonracehorses.

18F-sodium fluoride (18F-NaF) positron emission tomography (PET) has been validated as a useful imaging technique in the racehorse fetlock. The use of 18F-NaF PET in the nonracehorse fetlock has not been reported. To describe 18F-NaF PET findings in nonracehorse fetlocks, to compare with computed tomography (CT) findings and to compare PET findings between horses with and without fetlock pain. Retrospective observational study. All horses undergoing 18F-NaF PET and CT imaging of the fetlock between October 2016 and March 2021 were included in the study. Medical records were reviewed for associated lameness information. Thirty-six fetlocks (33 front and 3 hind) from 25 horses were included. The interobserver agreement for PET [0.62 (95% confidence interval [CI] 0.59-0.65)] was higher than for CT [0.47 (95% CI 0.43-0.51)]. Increased 18F-NaF uptake was most common in the medial subchondral bone of the proximal phalanx (23/36), the dorsomedial (20/36) and dorsosagittal (16/36) metacarpal/metatarsal distal subchondral bone, whereas sclerosis was identified on CT in these areas in 22 of 36 (p > 0.9), 33 of 36 (p = 0.001) and 23 of 36 (p = 0.15), respectively. Significant correlations were found between PET grades and both subchondral sclerosis and resorption CT grades (p < 0.001, Spearman r = 0.19 and 0.21, respectively). Abnormal 18F-NaF uptake in the proximal sesamoid bones (PSBs) was identified in 12 of 36 of the fetlocks, which was more common than CT abnormalities (3/36, p = 0.02). Periarticular increased uptake was seen in 7 of 36 fetlocks, whereas osteophytosis was recognised on CT in 20 of 36 (p = 0.1). Maximal standardised uptake values (SUVmax) were significantly higher in painful than in nonpainful fetlocks (22.0 and 11.9, respectively, p = 0.038). Retrospective study and limited sample size. Overall PET and CT findings follow a similar distribution in their location. PET identified more abnormalities in the PSBs than CT. SUVmax is a pertinent factor to take into consideration for the assessment of the clinical significance of findings.

Intra‑Articular Platelet‑Rich Plasma Injections VS Hyaluronic Acid for Patients with Knee Osteoarthritis: A Systematic Review

Introduction One of the most common conditions leading to impairment, particularly in the elderly, is osteoarthritis (OA). Most often caused by knee and/or hip OA, OA is the most prevalent articular disease in the developed world and a major contributor to chronic. OA is recognized as a major contributor to disability and impairment, and it has a significant socioeconomic cost due to medical and surgical procedures, as well as lost productivity. OA is a complex chronic illness that begins with joint cartilage disintegration and progresses to synovitis, subchondral sclerosis, and the development of peripheral osteophytes. A treatment option for osteoarthritis cartilage injuries is platelet-rich plasma (PRP) therapy, which is linked to a decrease in tissue inflammation. However, there is still a lack of clinical research on PRP administration's price, length of treatment, and possible application as a treatment for articular cartilage injuries. Objectives This study aimed to examine the clinical outcomes of patients with knee osteoarthritis, comparing the clinical results of The Western Ontario and McMaster Universities Arthritis Index (WOMAC) between PRP and HA intra-articular injection. Methods The medical term “PRP”, “HA”, and “Knee Osteoarthritis” were used in Pubmed and Google Scholar to discover studies of the efficacy of Intra‑articular PRP injection VS HA in decreasing WOMAC scores up to October 2023. Two independent reviewers excluded the non-RCTs and other clinical studies irrelevant to the study question. Seven remaining studies were reviewed and screened for inclusion based on relevance to the subject and outcomes. Results Based on seven studies in this review, two studies showed that intra-articular platelet-rich plasma has a superior outcome on decreasing the WOMAC score than intra-articular hyaluronic acid injection with significant. Five of seven studies demonstrated that PRP has better outcomes on WOMAC score, even if not significantly. Conclusions PRP intra-articular injection is a clinically meaningful improvement for patients with knee OA, with no significant difference between treatment groups

Development of Anti-OSCAR Antibodies for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease that causes local inflammation and pain, significantly reducing the quality of life and normal social activities of patients. Currently, there are no disease-modifying OA drugs (DMOADs) available, and treatment relies on pain relief agents or arthroplasty. To address this significant unmet medical need, we aimed to develop monoclonal antibodies that can block the osteoclast-associated receptor (OSCAR). Our recent study has revealed the importance of OSCAR in OA pathogenesis as a novel catabolic regulator that induces chondrocyte apoptosis and accelerates articular cartilage destruction. It was also shown that blocking OSCAR with a soluble OSCAR decoy receptor ameliorated OA in animal models. In this study, OSCAR-neutralizing monoclonal antibodies were isolated and optimized by phage display. These antibodies bind to and directly neutralize OSCAR, unlike the decoy receptor, which binds to the ubiquitously expressed collagen and may result in reduced efficacy or deleterious off-target effects. The DMOAD potential of the anti-OSCAR antibodies was assessed with in vitro cell-based assays and an in vivo OA model. The results demonstrated that the anti-OSCAR antibodies significantly reduced cartilage destruction and other OA signs, such as subchondral bone plate sclerosis and loss of hyaline cartilage. Hence, blocking OSCAR with a monoclonal antibody could be a promising treatment strategy for OA.

Treatment of symptomatic end-stage osteoarthritis of the ankle with anterolateral approach and an anatomical plate

The aim of this paper is to describe the anterolateral approach using an anatomical plate for ankle arthrodesis and to present the first mid-term results with this technique in ahigh-risk population. The indication for arthrodesis of the ankle joint with this described technique is moderate to severe osteoarthritis of the ankle. In addition to the general contraindications typical of any operation, there is a specific contraindication in cases of active infection of the soft tissues and accompanying osteomyelitis at the ankle. The incision is made along the course of the peroneus tertius muscle. After that, the mobilization of the peroneus superficialis nerve is carried out, followed by the mobilization of the long extensor tendons, especially the extensor digitorum muscle in amedial direction opening the capsule and removal of the residual cartilage on the distal tibia and talus. Subsequently, the subchondral sclerosis is opened, and the implantation of a suitable osteosynthesis material, e.g., an anatomical angle-stable plate, is carried out. Finally, wound closure is performed involving the muscle belly of the extensor digitorum muscle covering the plate. Immobilization of the ankle for 5-7days in adorsal knee-high splint. Retention in awalker after decongestion for another 5weeks. Increased loading can be done after X‑ray/computed tomography (CT) control from the 6thweek. In all, 11patients were observed retrospectively for an average of 14months. There were no complications. The European Foot and Ankle Society (EFAS) score improved significantly from 3.3 to 17.8 points. All patients were subjectively satisfied with the result and would have the operation again.

Betulinic Acid Attenuates Osteoarthritis via Limiting NLRP3 Inflammasome Activation to Decrease Interleukin-1β Maturation and Secretion.

Osteoarthritis (OA) is the most common degenerative joint disorder. Prior studies revealed that activation of NLRP3 inflammasome could promote the activation and secretion of interleukin-1β (IL-1β), which has an adverse effect on the progression of OA. Betulinic acid (BA) is a compound extract of birch, whether it can protect against OA and the mechanisms involved are still unknown. In vivo experiments, using gait analysis, ELISA, micro-CT, and scanning electron microscopy (SEM), histological staining, immunohistological (IHC) and immunofluorescence (IF) staining, and atomic force microscopy (AFM) to assess OA progression after intraperitoneal injection of 5 and 15 mg/kg BA in an OA mouse model. In vitro experiments, caspase-1, IL-1β, and the N-terminal fragment of gasdermin D (GSDMD-NT) were measured in bone marrow-derived macrophages (BMDMs) by using ELISA, western blot, and immunofluorescence staining. We demonstrated that OA progression can be postponed with intraperitoneal injection of 5 and 15 mg/kg BA in an OA mouse model. Specifically, BA postponed DMM-induced cartilage deterioration, alleviated subchondral bone sclerosis, and relieved synovial inflammation. In vitro studies, the activated NLRP3 inflammasome produces mature IL-1β by facilitating the cleavage of pro-IL-1β, and BA could inhibit the activation of NLRP3 inflammasome in BMDMs. Taken together, our analyses revealed that BA attenuates OA via limiting NLRP3 inflammasome activation to decrease the IL-1β maturation and secretion.

Retuning Mitochondrial Apoptosis/Mitophagy Balance via SIRT3-Energized and Microenvironment-Modulated Hydrogel Microspheres to Impede Osteoarthritis.

Full-range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)-tissues (cartilage)-cells (chondrocytes)-organelles cascade, of which the subcellular mitochondria dominate eukaryotic cells' fate, and thus causally influence OA progression. However, the dynamic regulation of mitochondrial rise and demise in impaired chondrocytes and the exact role of mitochondrial metronome sirtuins 3 (SIRT3) is not clarified. Herein, chondrocytes are treated with SIRT3 natural agonist dihydromyricetin (DMY) or chemical antagonist 3-TYP, respectively, to demonstrate the positive action of SIRT3 on preserving cartilage extracellular matrix (ECM). Molecular mechanical investigations disclose that SIRT3-induced chondroprotection depended on the repression of mitochondrial apoptosis (mtApoptosis) and the activation of mitophagy. Inspired by the high-level matrix proteinases and reactive oxygen species (ROS) in the OA environment, by anchoring gelatin methacrylate (GelMA) and benzenediboronic acid (PBA) to hyaluronic acid methacrylate (HAMA) with microfluidic technology, a dual-responsive hydrogel microsphere laden with DMY is tactfully fabricated and named as DMY@HAMA-GelMA-PBA (DMY@HGP). In vivo injection of DMY@HGP ameliorated cartilage abrasion and subchondral bone sclerosis, as well as promoted motor function recovery in post-traumatic OA (PTOA) model via recouping endogenous mtApoptosis and mitophagy balance. Overall, this study unveils a novel mitochondrial dynamic-oriented strategy, holding great promise for the precision treatment of OA.

Osteomodulin downregulation is associated with osteoarthritis development

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.

Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis

Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor antagonist (rimegepant) could suppress OA progression and relieve pain in two OA models. C57BL/6 mice (10-week-old) underwent surgical destabilization of the medial meniscus, and Rimegepant (1.0 mg/kg/100 μL) or phosphate-buffered saline (100 μL) was administered weekly intraperitoneally after OA surgery and evaluated at 4, 8, and 12 weeks. In the senescence-accelerated mice (SAM)-prone 8 (SAMP8), rimegepant was administered weekly before and after subchondral bone sclerosis and sacrificed at 9 and 23 weeks, respectively. Behavioral assessment and immunohistochemical staining (CGRP) of the dorsal root ganglion (DRG) were conducted to assess pain. In DMM mice, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed in the rimegepant group. In SAMP8, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed by rimegepant at 9 weeks; however, not at 23 weeks. Behavioral assessment shows the traveled distance and the number of standings in the rimegepant group were significantly longer and higher. In addition, CGRP expression of the DRG was significantly lower in the rimegepant group at 8 and 12 weeks of DMM and 9 weeks of SAMP8 treatment. No adverse effects were observed in either of the mouse models. Inhibition of CGRP signaling has the potential to be a therapeutic target to prevent OA progression and suppress pain through the attenuation of subchondral bone sclerosis and synovitis.

Features of Knee and Multijoint Osteoarthritis by Sex and Race and Ethnicity: A Preliminary Analysis in the Johnston County Health Study.

To evaluate knee osteoarthritis (KOA) and multijoint osteoarthritis (MJOA), and to compare features by sex and race and ethnicity in a population-based cohort. Participants (n = 544) enrolled in the Johnston County Health Study (JoCoHS) as of January 2023 were categorized by radiographic and symptomatic KOA and MJOA phenotypes, and frequencies were compared by sex and race and ethnicity. Symptoms were assessed according to the Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain, aching, and stiffness (PAS) scores at various joints. Models produced estimates (odds ratio [OR] or mean ratios [MR] and 95% CI) adjusted for age, BMI (kg/m2), and education. Men had twice the odds of having MJOA-6 (≥ 3 lower extremity joints affected); there were no significant differences in MJOA phenotypes by race and ethnicity. Women had 50% higher odds of having KOA or having various features of KOA. Women reported significantly worse KOOS Symptoms scores (MR 1.25). Black participants had higher odds of more severe KOA (OR 1.47), subchondral sclerosis (OR 2.06), and medial tibial osteophytes (OR 1.50). Black participants reported worse KOOS Symptoms than White participants (MR 1.18). Although not statistically significant, Hispanic participants (vs non-Hispanic participants) appeared to have lower odds of radiographic changes but reported worse symptoms. Preliminary findings in the diverse JoCoHS cohort suggest more lower extremity- predominant MJOA in men compared to women. Women and Black participants had more KOA features and more severe symptoms. Hispanic participants appear to have higher pain and symptoms scores despite having fewer structural changes. Studies in diverse populations are needed to understand the burden of OA.

Three-Dimensional Imaging and Histopathological Features of Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove Fissures in Thoroughbred Horses.

Fissure in the third metacarpal/tarsal parasagittal groove and proximal phalanx sagittal groove is a potential prodromal pathology of fracture; therefore, early identification and characterisation of fissures using non-invasive imaging could be of clinical value. Thirty-three equine cadaver limbs underwent standing cone-beam (CB) computed tomography (CT), fan-beam (FB) CT, low-field magnetic resonance imaging (MRI), and macro/histo-pathological examination. Imaging diagnoses of fissures were compared to microscopic examination. Imaging features of fissures were described. Histopathological findings were scored and compared between locations with and without fissures on CT. Microscopic examination identified 114/291 locations with fissures. The diagnostic sensitivity and specificity were 88.5% and 61.3% for CBCT, 84.1% and 72.3% for FBCT, and 43.6% and 85.2% for MRI. Four types of imaging features of fissures were characterised on CT: (1) CBCT/FBCT hypoattenuating linear defects, (2) CBCT/FBCT striated hypoattenuated lines, (3) CBCT/FBCT subchondral irregularity, and (4) CBCT striated hypoattenuating lines and FBCT subchondral irregularity. Fissures on MRI appeared as subchondral bone hypo-/hyperintense defects. Microscopic scores of subchondral bone sclerosis, microcracks, and collapse were significantly higher in locations with CT-identified fissures. All imaging modalities were able to identify fissures. Fissures identified on CT were associated with histopathology of fatigue injuries.

Asymmetric Load Transmission Induces Facet Joint Subchondral Sclerosis and Hypertrophy in Patients with Idiopathic Adolescent Scoliosis: Evaluation Using Finite Element Model and Surgical Specimen.

Adolescent idiopathic scoliosis (AIS) with thoracic curvature primarily progresses from the thoracolumbar region, causing abnormal twisting and rotation of the spinal column. This results in unbalanced, asymmetric loads on each vertebrae and increased demands on the thoracic facet joints to withstand rotational stress from adjacent vertebrae. However, no studies have focused on the stress distribution on the facet joints of the thoracic spine in patients with AIS. This study aimed to investigate the mechanical loading and its distribution on the thoracic facet joints of AIS patients using finite element (FE) analysis and surgical specimens. FE models of the thoracic spine were created from a total of 13 female AIS patients (Lenke type 1, n = 4; Lenke type 2, n = 4; Lenke type 3, n = 5). A load of 200 N on the T3 vertebrae and 30 N each on the bilateral superior articular processes were applied vertically to quantify the contact force on the facet joints from T3 to T11. In addition, morphological and histological analyses were performed on the inferior articular processes obtained during surgery. FE analysis demonstrated that contact forces of the facet joint progressively increased from the mid to lower thoracic spine of the concave side, reaching a maximum around the apex. More than 91% of the load was transmitted by the facet joints at the concave side, resulting in facet joint subchondral sclerosis and hypertrophy. The apical facet joint in AIS helps counteract rotational stress between vertebrae and transfers most stress through the concave side. In conclusion, this study found that asymmetric load transfer in the facet joints leads to subchondral sclerosis and hypertrophy. These findings can enhance our understanding of the stress loading on facet joints and the resulting biological changes and help clarify the mechanisms involved in scoliosis progression. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Much lower prevalence and severity of spine degenerative changes among older Chinese women than among older Caucasian women and its implication for the interpretation of lumbar spine BMD T-score for Chinese women.

The prevalence and severity of spine degenerative changes have been noted to be lower among older Chinese women than among older Caucasian women. Spine degenerative changes associated with marginal osteophytosis, trabecular thickening, subchondral sclerosis, facet joint arthrosis, and disc space narrowing can all lead to artificially higher spine areal bone mineral density (BMD). The lower prevalence and severity of spine degeneration have important implications for the interpretation of spine areal BMD reading for Chinese women. With fewer contributions from spine degenerative changes, following natural aging, the declines of population group means of spine BMD and T-score are faster for Chinese women than for Caucasian women. While a cutpoint T-score ≤ -2.5 for defining spine densitometric osteoporosis is recommended for Caucasian women, for Chinese women the same cutpoint T-score of ≤ -2.5 inflates the estimated osteoporosis prevalence based on spine BMD measure. In addition to the use of an ethnicity-specific BMD reference database, a stricter cutpoint T-score for defining spine densitometric osteoporosis among older Chinese women should be applied.

Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice

ObjectivesPrior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect...

Association between Modic changes and intervertebral vacuum phenomenon severity in patients undergoing percutaneous cement discoplasty.

Modic changes and intervertebral vacuum phenomenon (IVP) are considered spinal degenerative changes. The correlation between Modic and IVP has not been analyzed in the literature. To analyze the correlation between IVP severity, Modic changes, and subchondral sclerosis across the lumbar spine in patients with lumbar degeneration. This is a retrospective study analyzing patients who underwent percutaneous cement discoplasty at a single institution between 2015 and 2020. Preoperative magnetic resonance imaging and computed tomography scans were analyzed to make the measurements. Modic type and grade as well as severity of IVP were preoperatively measured. The association between Modic type, grade, subchondral sclerosis, and the presence of IVP was analyzed. In total, 110 patients (mean age = 77.03 ± 7.1 years) were finally included in the study. Per level correlation analysis showed a significant positive association between IVP and Modic type, IVP and Modic grade, and IVP and subchondral sclerosis. Moreover, subchondral sclerosis was significantly associated with Modic type and grade. Our study showed a significant positive correlation among Modic changes, IVP, and subchondral sclerosis throughout the lumbar spine. Our findings support the theory that endplate degeneration parameters are associated with the presence and severity of IVP.

Pentraxin 3 deficiency ameliorates the severity of osteoarthritis and alleviates inflammation

BackgroundOsteoarthritis is one of the most common degenerative joint disorders, characterized by articular cartilage breakdown, synovitis, osteophytes generation and subchondral bone sclerosis. Pentraxin 3 (PTX3) is a long pentraxin protein, secreted by immune cells, and PTX3 is identified to play a critical role in inflammation and macrophage polarization. However, the underlying mechanism of PTX3 in osteoarthritis under the circumstance of Ptx3-knockout (KO) mice model is still unknown. MethodsMurine destabilization of the medial meniscus (DMM) OA model was created in Ptx3-knockout (KO) and wildtype mice, respectively. The degenerative status of cartilage was detected by Safranin O, H&E staining, immunohistochemistry (IHC) and micro-CT. OARSI scoring was employed to assess the proteoglycan of cartilage. Serum inflammatory cytokines were examined by ELISA and systematic macrophage polarization in spleen was analyzed by flow cytometry. ResultsSafranin O and H&E staining confirmed that the joint cartilage was mostly with reduced degeneration in both the senior KO mice and the DMM model generated from the KO mice, compared to the WT group. This is also supported by micro-CT examination and OARSI scoring. Immunohistochemistry illustrated an up-regulation of Aggrecan and Collagen 2 and down-regulation of ADAMTS-5 and MMP13 in KO mice in comparison with the WT mice. ELISA indicated a dramatical decrease in the serum levels of TNF-α and IL-6 in KO mice. Polarization of M2-like macrophages was observed in the KO group. ConclusionPentraxin 3 deficiency significantly ameliorated the severity of osteoarthritis by preventing cartilage degeneration and alleviated systematic inflammation by inducing M2 polarization.

Disease-modifying interactions between chronic kidney disease and osteoarthritis: a new comorbid mouse model

ObjectiveThe prevalence of comorbid chronic kidney disease (CKD) and osteoarthritis (OA) is increasing globally. While sharing common risk factors, the mechanism and consequences of concurrent CKD-OA are unclear. The aims...

Multiple roles of ALK3 in osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

DOES THE FALSE PROFILE VIEW REALLY SHOW ANTERIOR COVER?

To quantify the acetabular coverage of the femoral head, Lequesne's vertical-center-anterior edge (VCA) angle is used on the false profile view. Lateral coverage is determined by Wiberg's lateral-center-edge (LCE) angle on an ap pelvic view. The delimitation of the weightbearing area is defined by the end of the subchondral sclerosis line for both views. To our knowledge the exact anatomic location of the points used for measurement on the acetabular rim are not known.Six hips from three cadaver pelvises (3 male and 3 female) were investigated. The anterior and lateral points of interested were identified radiographically using fluoroscopy and marked with 1mm ceramic bullets. Standard false profile views and ap pelvic views in neutral inclination and rotation were taken to check the correct location of the ceramic bullets. A CT of each pelvis was made to locate the ceramic bullets and to define the exact anatomic location of the measurement points on the o'clock position. 6 o‘clock was defined as the midpoint between anteroinferior and the posteroinferior rim edges. Values were normalized for a right hip.The mean clockface location for the VCA was 1:33 (range, 1:15 to 1:40) and for the LCE 0:38 (range, 0:20 to 0:50).The LCEA is slightly anterior to the 12 o'clock position and remains useful to quantify the lateral coverage. Surprisingly, the point used for measuring the VCA is only about 30° (1h) anterior of the point used for measuring the LCEA. Its value for determining anterior cover has to be questioned. The discrepancy to other studies in the literature is because this study identifies and measures the end of the weight bearing zone, and not the border of the bony acetabulum.

MicroRNA-224-5p nanoparticles balance homeostasis via inhibiting cartilage degeneration and synovial inflammation for synergistic alleviation of osteoarthritis

MicroRNAs play a crucial role in regulating cartilage extracellular matrix (ECM) metabolism and are being explored as potential therapeutic targets for osteoarthritis (OA). The present study indicated that microRNA-224-5p (miR-224-5p) could balance the homeostasis of OA via regulating cartilage degradation and synovium inflammatory simultaneously. Multifunctional polyamidoamine dendrimer with amino acids used as efficient vector to deliver miR-224-5p. The vector could condense miR-224-5p into transfected nanoparticles, which showed higher cellular uptake and transfection efficiency compared to lipofectamine 3000, and also protected miR-224-5p from RNase degradation. After treatment with the nanoparticles, the chondrocytes showed an increase in autophagy rate and ECM anabolic components, as evidenced by the upregulation of autophagy-related proteins and OA-related anabolic mediators. This led to a corresponding inhibition of cell apoptosis and ECM catabolic proteases, ultimately resulting in the alleviation of ECM degradation. In addition, miR-224-5p also inhibited human umbilical vein endothelial cells angiogenesis and fibroblast-like synoviocytes inflammatory hyperplasia. Integrating the above synergistic effects of miR-224-5p in regulating homeostasis, intra-articular injection of nanoparticles performed outstanding therapeutic effect by reducing articular space width narrowing, osteophyte formation, subchondral bone sclerosis and inhibiting synovial hypertrophy and proliferation in the established mouse OA model. The present study provides a new therapy target and an efficient intra-articular delivery method for improving OA therapy. Statement of significanceOsteoarthritis (OA) is the most prevalent joint disease worldwide. Gene therapy, which involves delivering microRNAs, has the potential to treat OA. In this study, we demonstrated that miR-224-5p can simultaneously regulate cartilage degradation and synovium inflammation, thereby restoring homeostasis in OA gene therapy. Moreover, compared to traditional transfection reagents such as lipofectamine 3000, G5-AHP showed better efficacy in both microRNA transfection and protection against degradation due to its specific surface structure. In summary, G5-AHP/miR-224-5p was developed to meet the clinical needs of OA patients and the high requirement of gene transfection efficiency, providing a promising paradigm for the future application and development of gene therapy.