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BioRxiv : the Preprint Server For... Jun 2024Cartilage plays a crucial role in skeletal development and function, and abnormal development contributes to genetic and age-related skeletal disease. To better...
UNLABELLED
Cartilage plays a crucial role in skeletal development and function, and abnormal development contributes to genetic and age-related skeletal disease. To better understand how human cartilage develops , we jointly profiled the transcriptome and open chromatin regions in individual nuclei recovered from distal femurs at 2 fetal timepoints. We used these multiomic data to identify transcription factors expressed in distinct chondrocyte subtypes, link accessible regulatory elements with gene expression, and predict transcription factor-based regulatory networks that are important for growth plate or epiphyseal chondrocyte differentiation. We developed a human pluripotent stem cell platform for interrogating the function of predicted transcription factors during chondrocyte differentiation and used it to test . We expect new regulatory networks we uncovered using multiomic data to be important for promoting cartilage health and treating disease, and our platform to be a useful tool for studying cartilage development .
STATEMENT OF SIGNIFICANCE
The identity and integrity of the articular cartilage lining our joints are crucial to pain-free activities of daily living. Here we identified a gene regulatory landscape of human chondrogenesis at single cell resolution, which is expected to open new avenues of research aimed at mitigating cartilage diseases that affect hundreds of millions of individuals world-wide.
PubMed: 38915712
DOI: 10.1101/2024.06.12.598666 -
BioRxiv : the Preprint Server For... Jun 2024Articular chondrocytes synthesize and maintain the avascular and aneural articular cartilage. these cells are surrounded by a 3D pericellular matrix (PCM) containing...
Articular chondrocytes synthesize and maintain the avascular and aneural articular cartilage. these cells are surrounded by a 3D pericellular matrix (PCM) containing predominantly collagen VI. The PCM protects chondrocytes and facilitates mechanotransduction, and PCM stiffness is critical in transmitting biomechanical signals to chondrocytes. Various culture systems with different hydrogels have been used to encapsulate chondrocytes for 3D culture, but many lack either the PCM or the stiffness of the cartilage matrix. Here, we demonstrate that primary chondrocytes cultured in alginate will form a pericellular matrix and display a phenotype similar to conditions. We found that primary human and bovine chondrocytes, when cultured in alginate beads with addition of sodium L-ascorbate for 7 days, had a pronounced PCM, retained their phenotype, and synthesized both collagens VI and II. This novel culture system enables alginate-encapsulated chondrocytes to develop a robust PCM thereby creating a model system to study mechanotransduction. We also observed distinct compression-induced changes in metabolomic profiles between the monolayer-agarose and alginate-released agarose-embedded chondrocytes indicating physiological changes in cell metabolism. Our data suggest that 3D preculture of chondrocytes in alginate before encapsulation in physiologically-stiff agarose leads to a pronounced development of pericellular matrix that is sustained in the presence of ascorbate. This novel model can be useful in studying the mechanism by which chondrocytes respond to cyclical compression and other types of loading simulating physiological conditions.
PubMed: 38915493
DOI: 10.1101/2024.06.10.598340 -
Journal of Orthopaedic Surgery and... Jun 2024The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using... (Meta-Analysis)
Meta-Analysis
PURPOSE
The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate.
METHODS
We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted.
RESULTS
A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = - 2.825, 95% CI - 3.343 to - 2.306, P < 0.001), (SMD = 2.73, 95% CI 1.60 to 3.86, P < 0.001), (SMD = 0.85, 95% CI 0.5 to 1.2, P < 0.001) respectively compared to preoperative values. The surgery failure rate was 11% (95% CI 8-15%), with a total of 12 patients experiencing complications.
CONCLUSION
The use of AMIC demonstrates a positive impact on pain management, functional improvement, and mobility enhancement in patients with OLT. It is worth noting that the choice of stent for AMIC, patient age, and OLT size can influence the ultimate clinical outcomes. This study provides evidences supporting the safety and efficacy of AMIC as a viable treatment option in real-world medical practice.
Topics: Humans; Talus; Chondrogenesis; Transplantation, Autologous; Treatment Outcome; Time Factors; Cartilage, Articular
PubMed: 38915104
DOI: 10.1186/s13018-024-04864-z -
Arthroscopy : the Journal of... Jun 2024To investigate reoperation rates after meniscus allograft transplant (MAT), comparing rates with and without concomitant articular cartilage and osteotomy procedures...
PURPOSE
To investigate reoperation rates after meniscus allograft transplant (MAT), comparing rates with and without concomitant articular cartilage and osteotomy procedures using a national insurance claims database.
METHODS
We performed a retrospective cohort study of patients who underwent MAT from 2010 to 2021 with minimum 2 year follow-up using the PearlDiver database. Using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) codes, we identified patients who underwent concomitant procedures including chondroplasty or microfracture, cartilage restoration defined as osteochondral graft or autologous chondrocyte implantation (ACI), or osteotomy. Univariate logistic regressions identified risk factors for reoperation. Reoperations were classified as knee arthroplasty, interventional procedures, or diagnostic or debridement procedures.
RESULTS
750 patients were included with an average age of 29.6 years (interquartile range 21.0-36.8) and average follow-up time was 5.41 years (SD: 2.51). 90-day, 2-year, and all-time reoperation rates were 1.33%, 14.4%, and 27.6% respectively. MAT with cartilage restoration was associated with increased reoperation rate at 90 days (OR: 4.88; 95% CI: 1.38-19.27; p=.015), however there was no significant difference in reoperation rates at 2 years or to the end of follow-up. ACI had increased reoperation rates at 90 days (OR: 6.95; 95% CI: 1.45-25.96; p=.006), with no difference in reoperation rates 2 years post-operatively or to the end of follow-up. Osteochondral autograft and allograft were not associated with increased reoperation rates.
CONCLUSION
14.4% of patients in our cohort had a reoperation within 2 years of MAT. Nearly one in four patients undergoing MAT had concomitant cartilage restoration, showing that it is commonly performed on patients with articular cartilage damage. Concomitant osteochondral autograft, osteochondral allograft, chondroplasty, microfracture and osteotomy were not associated with any significant difference in reoperation rates. ACI was associated with increased reoperation rates at 90 days, but not later.
PubMed: 38914300
DOI: 10.1016/j.arthro.2024.06.022 -
Stem Cells Translational Medicine Jun 2024Mesenchymal stem cells (MSCs) offer great potential for treatment of osteoarthritis (OA) by promoting articular cartilage regeneration via paracrine secretion of...
Mesenchymal stem cells (MSCs) offer great potential for treatment of osteoarthritis (OA) by promoting articular cartilage regeneration via paracrine secretion of exosomes; however, the underlying mechanisms are not fully understood. This study aimed to explore the therapeutic effects of exosomes secreted by human umbilical cord-derived MSCs (hUC-MSCs) in rat models of OA and reveal the underlying mechanisms. UC-MSCs and UC-MSC-exosomes were prepared and identified by transmission electron microscopy and flow cytometry. IL-1β-induced OA chondrocytes and the operation and collagenase-induced OA rat models were established. The results of micro-computed tomography, histology, and immunohistochemistry showed that UC-MSC-exosomes promoted cartilage regeneration in OA rats. ELISA results showed that the levels of synovial fluid cytokines, TNF-α, IL-1β, and IL-6, were lower in exosome therapy group than control group in both OA rat models. Exosome treatment significantly downregulated the expression of MMP-13 and ADAMTS-5 in chondrocytes stimulated by IL-1β, and upregulated collagen II expression. These findings suggest that hUC-MSC-exosomes offer a promising option for the therapy for OA.
PubMed: 38913985
DOI: 10.1093/stcltm/szae031 -
Biomolecules & Biomedicine Jun 2024Knee osteoarthritis (KOA) is one of the most common degenerative joint diseases in the elderly worldwide. The primary lesion in patients with KOA is the degeneration of...
Knee osteoarthritis (KOA) is one of the most common degenerative joint diseases in the elderly worldwide. The primary lesion in patients with KOA is the degeneration of articular cartilage. This study aimed to observe the biological effects of cyclic negative pressure on C28/I2 chondrocytes and to elucidate the underlying molecular mechanisms. We designed a bi-directional intelligent micro-pressure control device for cyclic negative pressure intervention on C28/I2 chondrocytes. Chondrocyte vitality and proliferation were assessed using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. The extracellular matrix was analyzed using real-time fluorescence quantitative polymerase chain reaction (PCR) and western blot, while the molecular mechanism of the chondrocyte response to cyclic negative pressure was explored through mRNA sequencing. Experimental data demonstrated that cyclic negative pressure promoted chondrocyte proliferation and upregulated the expression of chondrocyte-specific protein, namely the collagen type II alpha 1 chain (COL2A1) protein, and the transcription factor SRY-box transcription factor 9 (SOX9). Additionally, RNA sequencing analysis revealed that the gene levels of insulin-like growth factor 2 (IGF-2) and early growth response 1 (EGR-1) were significantly elevated in the cyclic negative pressure group. This study demonstrates that cyclic negative pressure stimulates the proliferation of C28/I2 chondrocytes by promoting the expression of EGR-1 and IGF-2. This new discovery may provide novel insights into cartilage health and KOA prevention.
PubMed: 38912889
DOI: 10.17305/bb.2024.10487 -
Cureus Jun 2024Articular cartilage defects are common injuries of the knee. The defects often progress in size and produce significant clinical symptoms due to the lack of intrinsic...
Articular cartilage defects are common injuries of the knee. The defects often progress in size and produce significant clinical symptoms due to the lack of intrinsic repair or regenerative capacity of articular cartilage. With the failure of nonoperative treatment options, surgical treatment is indicated and includes palliative, reparative, and regenerative options. For large defects of the femoral condyles, trochlea, or patella, autologous chondrocyte implantation can provide successful and long-lasting results. Presented is the case of a 37-year-old male with an 18-year follow-up to autologous chondrocyte implantation for extensive left knee articular cartilage defects of the medial and lateral femoral condyles. Recovery from articular cartilage defects is shown through both clinical improvement of the patient and arthroscopic photographs of robust autologous articular cartilage on the medial femoral condyle. This case supports the long-term benefits of autologous chondrocyte implantation as a surgical intervention for large, full-thickness articular cartilage defects of the knee.
PubMed: 38912077
DOI: 10.7759/cureus.62913 -
Revista Brasileira de Ortopedia Jun 2024Knee osteoarthritis (OA) is an inflammatory and degenerative condition resulting in articular cartilage destruction and functional loss. Its prevalence has grown...
Knee osteoarthritis (OA) is an inflammatory and degenerative condition resulting in articular cartilage destruction and functional loss. Its prevalence has grown considerably due to increased life expectancy and obesity, and its diagnosis relies on evaluation, medical examination, and confirmation by supplementary radiographic images. Knee OA is multifactorial and influenced by several local, systemic, and external aspects. In addition, its progress and therapeutic responses highly depend on the characteristics of each subject. The initial recommendation is drug treatment and alternative therapies to improve quality of life. However, if these treatments are unsuccessful, one must consider surgical treatment. Surgical options include arthroscopies, osteotomies, and partial and total arthroplasties, while non-surgical treatments include medications and alternative therapies such as infiltrations, acupuncture, and physical exercise. It is worth highlighting that biomarkers can be a significant strategy for early disease detection, assessment of disease activity, prediction of prognosis, and monitoring a better response to therapy. Nevertheless, this topic must be the focus of further research to confirm its findings.
PubMed: 38911892
DOI: 10.1055/s-0044-1786351 -
Annals of Translational Medicine Jun 2024Several tissues contribute to the onset and advancement of knee osteoarthritis (OA). One tissue type that is worthy of closer evaluation, particularly in the context of...
BACKGROUND
Several tissues contribute to the onset and advancement of knee osteoarthritis (OA). One tissue type that is worthy of closer evaluation, particularly in the context of sex, is the infrapatellar fat pad (IFP). We previously demonstrated that removal of the IFP had short-term beneficial effects for a cohort of male Dunkin-Hartley guinea pigs. The present project was designed to elucidate the influence of IFP removal in females of this OA-prone strain. It was hypothesized that resection of the IFP would reduce the development of OA in knees of a rodent model predisposed to the disease.
METHODS
Female guinea pigs (n=16) were acquired at an age of 2.5 months. Surgical removal of the IFP and associated synovium complex (IFP/SC) was executed at 3 months of age. One knee had the IFP/SC resected; a comparable sham surgery was performed on the contralateral knee. All animals were subjected to voluntary enclosure monitoring and dynamic weight-bearing, as well as compulsory treadmill-based gait analysis monthly; baseline data was collected prior to surgery. Guinea pigs were euthanized at 7 months. Knees from eight animals were evaluated via histology, mRNA expression, and immunohistochemistry (IHC); knees from the remaining eight animals were allocated to microcomputed tomography (microCT), biomechanical analyses (whole joint testing and indentation relaxation testing), and atomic absorption spectroscopy (AAS).
RESULTS
Fibrous connective tissue (FCT) replaced the IFP/SC. Mobility/gait data indicated that unilateral IFP/SC removal did not affect bilateral hindlimb movement. MicroCT demonstrated that osteophytes were not a significant feature of OA in this sex; however, trabecular thickness (TbTh) in medial femorae decreased in knees containing the FCT. Histopathology scores were predominantly influenced by changes in the lateral tibia, which demonstrated that histologic signs of OA were increased in knees containing the native IFP/SC versus those with the FCT. Similarly, indentation testing demonstrated higher instantaneous and equilibrium moduli in the lateral tibial articular cartilage of control knees with native IFPs. AAS of multiple tissue types associated with the knee revealed that zinc was the major trace element influenced by removal of the IFP/SC.
CONCLUSIONS
Our data suggest that the IFP/SC is a significant component driving knee OA in female guinea pigs and that resection of this tissue prior to disease has short-term benefits. Specifically, the formation of the FCT in place of the native tissue resulted in decreased cartilage-related OA changes, as demonstrated by reduced Osteoarthritis Research Society International (OARSI) histology scores, as well as changes in transcript, protein, and cartilage indentation analyses. Importantly, this model provides evidence that sex needs to be considered when investigating responses and associated mechanisms seen with this intervention.
PubMed: 38911554
DOI: 10.21037/atm-23-1886 -
The American Journal of Sports Medicine Jun 2024The outcomes of medial meniscal allograft transplantation (MMAT) combined with high tibial osteotomy (HTO) compared with isolated MMAT remain unclear.
BACKGROUND
The outcomes of medial meniscal allograft transplantation (MMAT) combined with high tibial osteotomy (HTO) compared with isolated MMAT remain unclear.
PURPOSE
To compare the clinical and radiological results of MMAT combined with HTO and isolated MMAT.
STUDY DESIGN
Cohort study; Level of evidence, 3.
METHODS
This retrospective study included 42 consecutive patients, who were divided into group M (isolated MMAT; n = 22) and group H (MMAT combined with HTO with a varus angle >3°; n = 20). Group differences in subjective knee scores, isokinetic muscle strength test, and radiological outcomes (Kellgren-Lawrence grade, mechanical axis, graft extrusion, graft status, and articular cartilage loss) were compared.
RESULTS
The mean follow-up period was 29.2 ± 4.9 months and 27.4 ± 5.3 months for groups M and H, respectively. The Lysholm score improved from 55.4 ± 9.5 to 81.3 ± 9.7 and from 52.6 ± 8.9 to 84.2 ± 10.2 in groups M and H, respectively (both < .001). The International Knee Documentation Committee subjective score improved from 51.4 ± 10.3 to 79.6 ± 9.4 and from 49.3 ± 11.4 to 81.4 ± 8.3 in groups M and H, respectively (both < .001). Both groups showed no significant differences in subjective knee scores and isokinetic extensor strength at the final follow-up. The rate of preoperative and postoperative high International Cartilage Regeneration & Joint Preservation Society grade (≥3) did not differ between the 2 groups. Group M showed greater coronal graft extrusion than did group H (3.3 ± 0.7 mm vs 2.7 ± 0.8 mm; = .014); the rate of pathologic graft extrusion (≥3 mm) was not higher in group M (40.9%) than in group H (20%) with the number of patients available ( = .143). Both groups showed no significant difference in the graft status. Graft tears were observed in 2 patients (9%) in group M and 1 patient (5%) in group H ( = .607).
CONCLUSION
Clinical scores significantly improved after isolated MMAT and MMAT combined with HTO compared with preoperative values, and their short-term outcomes were similar. Postoperative graft extrusion was greater in patients who underwent isolated MMAT, implying that active correction of varus alignment during MMAT may help in intra-articular biomechanics.
PubMed: 38910353
DOI: 10.1177/03635465241255346