-
Frontiers in Endocrinology 2024Osteoarthritis (OA) is an intricate pathological condition that primarily affects the entire synovial joint, especially the hip, hand, and knee joints. This results in... (Review)
Review
Osteoarthritis (OA) is an intricate pathological condition that primarily affects the entire synovial joint, especially the hip, hand, and knee joints. This results in inflammation in the synovium and osteochondral injuries, ultimately causing functional limitations and joint dysfunction. The key mechanism responsible for maintaining articular cartilage function is chondrocyte metabolism, which involves energy generation through glycolysis, oxidative phosphorylation, and other metabolic pathways. Some studies have shown that chondrocytes in OA exhibit increased glycolytic activity, leading to elevated lactate production and decreased cartilage matrix synthesis. In OA cartilage, chondrocytes display alterations in mitochondrial activity, such as decreased ATP generation and increased oxidative stress, which can contribute to cartilage deterioration. Chondrocyte metabolism also involves anabolic processes for extracellular matrix substrate production and energy generation. During OA, chondrocytes undergo considerable metabolic changes in different aspects, leading to articular cartilage homeostasis deterioration. Numerous studies have been carried out to provide tangible therapies for OA by using various models and targeting chondrocyte metabolism, although there are still certain limitations. With growing evidence indicating the essential role of chondrocyte metabolism in disease etiology, this literature review explores the metabolic characteristics and changes of chondrocytes in the presence of OA, both and . To provide insight into the complex metabolic reprogramming crucial in chondrocytes during OA progression, we investigate the dynamic interaction between metabolic pathways, such as glycolysis, lipid metabolism, and mitochondrial function. In addition, this review highlights prospective future research directions for novel approaches to diagnosis and treatment. Adopting a multifaceted strategy, our review aims to offer a comprehensive understanding of the metabolic intricacies within chondrocytes in OA, with the ultimate goal of identifying therapeutic targets capable of modulating chondrocyte metabolism for the treatment of OA.
Topics: Chondrocytes; Humans; Osteoarthritis; Animals; Cartilage, Articular; Glycolysis
PubMed: 38854686
DOI: 10.3389/fendo.2024.1393550 -
Orthopaedic Journal of Sports Medicine Jun 2024Most healthcare providers utilize magnetic resonance imaging (MRI) to assist in diagnosing and treating osteochondritis dissecans (OCD) of the capitellum. However,...
BACKGROUND
Most healthcare providers utilize magnetic resonance imaging (MRI) to assist in diagnosing and treating osteochondritis dissecans (OCD) of the capitellum. However, consensus on imaging features that portend clinically relevant information in the care of these lesions has not been determined.
PURPOSE
To conduct a survey on the MRI features of a capitellar OCD that are salient for clinical decision-making using a classic Delphi protocol.
STUDY DESIGN
A consensus statement.
METHODS
Invitations to participate were sent to 33 healthcare providers identified as capitellar OCD experts. A classic 3-round survey method was used to gather agreement and consensus on the level of importance for clinical decision-making on 33 MRI features. A concise list of features that guide decision-making on the stability of an OCD lesion and the ability of an OCD lesion to heal with nonoperative care was also identified. Agreement and consensus were determined a priori as ≥66%.
RESULTS
Of the 33 identified experts, 20 agreed to participate, and 17 (52%) completed all 3 rounds. Of the 33 MRI features evaluated, 17 reached agreement as important for clinical decision-making by the experts. Consensus was reached for a concise list of MRI features that were significant to decision-making (94%), suggestive of a stable lesion (100%), had the potential to heal with nonoperative treatment (94%), were suggestive of an unstable lesion (100%), and had low potential to heal with nonoperative treatment (88%).
CONCLUSION
This 3-round Delphi process produced consensus on clinically relevant MRI features that contribute to clinical decision-making for capitellar OCD. The results of this study will be used as the basis for an interrater reliability assessment of the identified salient features, creating the foundation for developing a reliable MRI assessment tool rooted in clinical experiences. The development of a standardized assessment of capitellar OCD is intended to improve clinical practice and patient outcomes.
PubMed: 38845610
DOI: 10.1177/23259671241252813 -
Arthroscopy : the Journal of... Jun 2024To assess clinical outcomes and return to sport (RTS) rates among patients that undergo osteochondral allograft (OCA) transplantation and autologous chondrocyte...
Comparable Clinical and Functional Outcomes Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint at a Mean Follow-up of 5 Years.
PURPOSE
To assess clinical outcomes and return to sport (RTS) rates among patients that undergo osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte implantation (MACI), for patellofemoral articular cartilage defects.
METHODS
A retrospective review of patients who underwent an OCA or ACI/MACI from 2010-2020 was conducted. Patient-reported outcomes (PROs) collected included: Visual Analog Scale for pain/satisfaction, Knee Injury and Osteoarthritis Outcome Score (KOOS), and RTS. The percentage of patients that met the Patient Acceptable Symptom State (PASS) for KOOS was recorded. Logistic regression was used to identify predictors of worse outcomes.
RESULTS
A total of 95 patients were included (78% follow-up) with ACI or MACI performed in 55 cases (57.9%) and OCA in 40 (42.1%). A tibial tubercle osteotomy was the most common concomitant procedure for OCA (66%) and ACI/MACI (98%). Overall, KOOS pain was significantly poorer in OCA than ACI/MACI (74.7, 95% CI [68.1, 81.1] vs 83.6, 95% CI [81.3, 88.4], p= 0.012), while the remaining KOOS subscores were non-significantly different (all p>0.05). Overall, RTS rate was 54%, with no significant difference in return between OCA or ACI/MACI (52% vs 58%, p= 0.738). There were 26 (27%) reoperations and 5 (5%) graft failures in the entire group. Increasing age was associated with lower satisfaction in OCA and poorer outcomes in ACI/MACI, while larger lesion area was associated with lower satisfaction and poorer outcomes in ACI/MACI.
CONCLUSION
Clinical and functional outcomes were similar in patients that underwent OCA or ACI/MACI for patellofemoral articular cartilage defects at a mean follow-up of 5 years. Patients who received OCA had a higher proportion of degenerative cartilage lesions and, among those with trochlear lesions, reported higher pain at final follow-up than their ACI/MACI counterparts. Overall, increasing age and a larger lesion size were associated with worse patient-reported outcomes.
PubMed: 38844011
DOI: 10.1016/j.arthro.2024.05.018 -
Journal of Bone and Mineral Research :... Jun 2024Histone deacetylase 3 (Hdac3) is an epigenetic regulator of gene expression and interacts with skeletal transcription factors such as Runx2. We previously reported that...
Histone deacetylase 3 (Hdac3) is an epigenetic regulator of gene expression and interacts with skeletal transcription factors such as Runx2. We previously reported that conditional deletion of Hdac3 in Osterix-Cre recombinase-expressing osteoprogenitor cells (Hdac3 CKOOsx) caused osteopenia and increased marrow adiposity, both hallmarks of skeletal aging. We also showed that Runx2+ cells within osteogenic cultures of Hdac3-depleted bone marrow stromal cells (BMSCs) contain lipid droplets (LDs). Cellular senescence, a non-proliferative metabolically active state, is associated with increased marrow adiposity, bone loss and aging. In this study, we sought to determine if Hdac3 depleted Runx2+ pre-osteoblasts from young mice exhibit chromatin changes associated with early cellular senescence and how these events correlate with the appearance of LDs. We first confirmed that BMSCs from Hdac3 CKOOsx mice have more Runx2 + LD+ cells compared to controls under osteogenic conditions. We then measured senescence-associated distention of satellite DNA (SADS) and telomere-associated foci (TAFs) in Hdac3 CKOOsx and control BMSCs. In situ, Runx2+ cells contained more SADs per nuclei in Hdac3 CKOOsx femora than in controls. Runx2+ BMSCs from Hdac3 CKOOsx mice also contained more SADS and TAFs per nuclei than Runx2+ cells from age-matched control mice in vitro. SADs and TAFs were present at similar levels in Runx2 + LD+ cells and Runx2 + LD- cells from Hdac3 CKOOsx mice. Hdac inhibitors also increased the number of SADS in Runx2 + LD+ and Runx2 + LD- wildtype BMSCs. Senolytics reduced viable cell numbers in Hdac3 CKOOsx BMSC cultures. These data demonstrate that depletion of Hdac3 in osteochondral progenitor cells triggers LD formation and early events in cellular senescence in Runx2+ BMSCs through mutually exclusive mechanisms.
PubMed: 38843356
DOI: 10.1093/jbmr/zjae085 -
Frontiers in Veterinary Science 2024Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint...
Case report: Equine metacarpophalangeal joint partial and full thickness defects treated with allogenic equine synovial membrane mesenchymal stem/stromal cell combined with umbilical cord mesenchymal stem/stromal cell conditioned medium.
Here, we describe a case of a 5-year-old show-jumping stallion presented with severe lameness, swelling, and pain on palpation of the left metacarpophalangeal joint (MCj). Diagnostic imaging revealed full and partial-thickness articular defects over the lateral condyle of the third metacarpus (MC3) and the dorsolateral aspect of the first phalanx (P1). After the lesion's arthroscopic curettage, the patient was subjected to an innovative regenerative treatment consisting of two intra-articular injections of equine synovial membrane mesenchymal stem/stromal cells (eSM-MSCs) combined with umbilical cord mesenchymal stem/stromal cells conditioned medium (UC-MSC CM), 15 days apart. A 12-week rehabilitation program was accomplished, and lameness, pain, and joint effusion were remarkably reduced; however, magnetic resonance imaging (MRI) and computed tomography (CT) scan presented incomplete healing of the MC3's lesion, prompting a second round of treatment. Subsequently, the horse achieved clinical soundness and returned to a higher level of athletic performance, and imaging exams revealed the absence of lesions at P1, fulfillment of the osteochondral lesion, and cartilage-like tissue formation at MC3's lesion site. The positive outcomes suggest the effectiveness of this combination for treating full and partial cartilage defects in horses. Multipotent mesenchymal stem/stromal cells (MSCs) and their bioactive factors compose a novel therapeutic approach for tissue regeneration and organ function restoration with anti-inflammatory and pro-regenerative impact through paracrine mechanisms.
PubMed: 38840629
DOI: 10.3389/fvets.2024.1403174 -
The Journal of Craniofacial Surgery Jun 2024This study introduces a novel application of the Osteochondral Autograft Transfer System (OATS) for autologous bone grafting during alveolar cleft repair. Approximately...
This study introduces a novel application of the Osteochondral Autograft Transfer System (OATS) for autologous bone grafting during alveolar cleft repair. Approximately 75% of patients with cleft lip and palate have an alveolar cleft, which often necessitates secondary bone grafting from common donor sites such as the iliac crest. Traditional harvesting techniques, although effective, can be labor-intensive and increase the risk of donor site injury. Here the authors describe the use of OATS, which has primarily been used in orthopedic procedures like anterior cruciate ligament reconstruction, for the first time in alveolar cleft repair. It involves a minimally invasive, single-use transfer system for harvesting osteochondral autografts from the anterior iliac crest, and thereby reduces harvest time compared with traditional open approaches. The procedure is detailed from pre-operative evaluation through long-term follow-up and highlights the technique's benefits related to surgical time, ease of use, and maintenance of sizable autograft volumes. Similarly, the authors discuss other advantages of OATS, including its single-use and cordless nature, which is believed to contribute to a lower contamination risk and better intraoperative ergonomics.
PubMed: 38836797
DOI: 10.1097/SCS.0000000000010399 -
Surgical and Radiologic Anatomy : SRA Jun 2024The aim of this study was to determine anatomical predictors for the occurrence of medial osteochondral lesions of the talus (OLT), by analyzing morphometric variables...
PURPOSE
The aim of this study was to determine anatomical predictors for the occurrence of medial osteochondral lesions of the talus (OLT), by analyzing morphometric variables obtained from magnetic resonance imaging (MRI).
METHODS
A total of 430 ankles with 215 ankle MRIs from patients with nontraumatic OLTs on the medial side of the talar dome and an equal number of age, sex, and side-matched healthy controls were analyzed in this retrospective study. The specific MRI parameters that were measured include the anterior opening angle of the talus (AOT), the angle between the tibial axis and medial malleolus (TMM), the angle of the tibial plafond to the malleoli (PMA), the angle between the anterior and posterior talofibular ligaments (ATFL-PTFL angle), length of the trochlea tali arc (TAL), sagittal length of distal tibial articular surface (TAS), the ratio of the sagittal length of distal tibial articular surface to the length of the trochlea tali arc (TAS/TAL), and the depth of the incisura fibularis (IncDep).
RESULTS
AOT, IncDep, ATFL-PTFL angle, PMA, TMM, TAL, and TAS/TAL exhibited significant differences between the two groups. The established cut-off values were 13° (AUC 0.875) for AOT, 3.7 mm (AUC 0.565) for IncDep, 78° (AUC 0.729) for ATFL-PTFL angle, 14° (AUC 0.581) for PMA, 15° (AUC 0.907) for TMM, 34.3 mm (AUC 0.599) for TAL, and 0.81 (AUC 0.719) for TAS/TAL. Multivariate logistic regression analysis revealed Odds Ratio (OR) = 22.22 for AOT > 13°, OR = 4.23 for ATFL-PTFL angle > 78°, OR = 1.99 for PMA ≤ 14°, OR = 31.598 for TMM > 15°, OR = 3.79 for TAS/TAL ≤ 0.81.
CONCLUSION
This study highlights the significance of anatomical parameters, particularly the TMM and AOT, as key predictors of OLT.
PubMed: 38834726
DOI: 10.1007/s00276-024-03397-8 -
Orthopaedic Journal of Sports Medicine Jun 2024Multiligament knee injuries (MLKI), rare in adolescents, are challenging injuries that require complex surgical reconstruction. Historically, nonanatomic reconstructions...
BACKGROUND
Multiligament knee injuries (MLKI), rare in adolescents, are challenging injuries that require complex surgical reconstruction. Historically, nonanatomic reconstructions have been associated with prolonged immobilization and failure to restore normal knee biomechanics, resulting in arthrofibrosis and high rates of graft failure.
PURPOSE
To describe the clinical and patient-reported outcomes (PROs) for adolescent patients treated with single-stage anatomic multiligament knee reconstruction.
STUDY DESIGN
Case series; Level of evidence, 4.
METHODS
A single-center retrospective study was performed of patients ≤18 years old who underwent reconstruction of MLKIs by a single surgeon between 2014 and 2019 using a single-stage anatomic technique, with protected weightbearing and early range of motion. Complications were defined as infection, arthrofibrosis, deep vein thrombosis (DVT) or pulmonary embolus, and secondary surgery. PROs, including the pediatric version of the International Knee Documentation Committee (Pedi-IKDC) and the Tegner activity score, were obtained at a minimum of 2 years postoperatively.
RESULTS
Included were 30 patients (21 male, 9 female; mean age, 15.4 years). The most common ligamentous reconstruction types were anterior cruciate ligament (ACL) + fibular collateral ligament (12 patients; 40%) and ACL + medial collateral ligament (9 patients; 30%). Three patients (10%) had secondary surgeries, including irrigation and debridement of a granuloma, a staged osteochondral allograft transplantation to a lateral femoral condyle impaction fracture, and repair of a medial meniscal tear and lateral femoral condyle fracture associated with new injuries 2 years after ACL + fibular collateral ligament reconstruction. Two patients (7%) developed arthrofibrosis and 1 patient (3%) developed DVT. PRO scores obtained at a mean of 37 months postoperatively included a mean Pedi-IKDC of 87 (range, 52-92) and a median highest Tegner score at any point postoperatively of 9 (range, 5-10). Of the patients who were athletes before their injury, 70% returned to the same or higher level of sport postoperatively.
CONCLUSION
Reconstruction of MLKI in this series of adolescents with single-stage anatomic techniques and early range of motion resulted in low rates of secondary surgery, few complications, and good knee function as well as PRO scores at mean 3-year follow-up.
PubMed: 38831875
DOI: 10.1177/23259671241252870 -
Journal of Children's Orthopaedics Jun 2024The purpose of this study is to assess clinical and functional outcomes in separate cohorts of operatively and nonoperatively managed pediatric patella fractures.
PURPOSE
The purpose of this study is to assess clinical and functional outcomes in separate cohorts of operatively and nonoperatively managed pediatric patella fractures.
METHODS
A retrospective review was completed for patients aged 5-19 years treated for a unilateral patella fracture at a single pediatric level-1 trauma center. Patients were excluded for osteochondral fracture associated with patellar dislocation, polytrauma presentation with additional fractures, or <3 months of clinical follow-up. Functional outcomes were assessed via the Pediatric International Knee Documentation Committee form and the Marx Knee Activity Scale.
RESULTS
A total of 53 patients met inclusion criteria; 30 patients were treated operatively and 23 patients were treated nonoperatively. Patients with patellar sleeve/pole fractures were significantly younger by 5.2 years (p < 0.01) and presented with greater variability in mechanism of injury (p < 0.01). The nonoperative cohort achieved bony healing and returned to sports at a median (interquartile range) of 1.7 (1.2-2.3) months and 2.8 (2.3-3.3) months, respectively, post-injury. The operative group achieved bony healing and returned to sports at 2.8 (2.1-3.5) months and 5.9 (4.0-7.1) months, respectively, following surgery. Median (interquartile range) Pediatric International Knee Documentation Committee and Marx scores were 98 (89-100) and 14 (10-16), respectively, for the nonoperative group, and 92 (84-99) and 13 (12-16), respectively, for the operative group. No significant differences in patient-reported outcomes were observed between fracture patterns or treatment cohorts.
CONCLUSION
Pediatric and adolescent patients sustaining patella fractures reported long-term functional outcomes comparable to normative values, across multiple fracture patterns and with appropriate operative and nonoperative treatment. Fractures requiring surgery were expectedly associated with slower healing and return to sport timelines.
LEVEL OF EVIDENCE
Therapeutic Level III.
PubMed: 38831855
DOI: 10.1177/18632521241232301 -
Stem Cell Research & Therapy Jun 2024Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically...
Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model.
INTRODUCTION
Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model.
METHODS
Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume.
RESULTS
In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect.
CONCLUSION
Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.
Topics: Animals; Rabbits; Platelet-Rich Plasma; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Adipose Tissue; Hydrogels
PubMed: 38831361
DOI: 10.1186/s13287-024-03750-z