Proteomic Analysis of Female Synovial Fluid to Identify Novel Biomarkers for Osteoarthritis.

Osteoarthritis (OA) is a highly prevalent degenerative joint condition that disproportionately affects females. The pathophysiology of the disease is not well understood, which makes diagnosis and treatment difficult. Given the physical connection of synovial fluid (SF) with articular tissues, the SF's composition can reflect relevant biological modifications, and has therefore been a focus of research.

Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis.

Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling.

Age-related increase of kynurenine enhances miR29b-1-5p to decrease both CXCL12 signaling and the epigenetic enzyme Hdac3 in bone marrow stromal cells.

Mechanisms leading to age-related reductions in bone formation and subsequent osteoporosis are still incompletely understood. We recently demonstrated that kynurenine (KYN), a tryptophan metabolite, accumulates in serum of aged mice and induces bone loss. Here, we report on novel mechanisms underlying KYN's detrimental effect on bone aging.

MicroRNA-141-3p Negatively Modulates SDF-1 Expression in Age-Dependent Pathophysiology of Human and Murine Bone Marrow Stromal Cells.

Stromal cell-derived factor-1 (SDF-1 or CXCL12) is a cytokine secreted by cells including bone marrow stromal cells (BMSCs). SDF-1 plays a vital role in BMSC migration, survival, and differentiation. Our group previously reported the role of SDF-1 in osteogenic differentiation in vitro and bone formation in vivo; however, our understanding of the post-transcriptional regulatory mechanism of SDF-1 remains poor.

Advances in Molecular biomarker for early diagnosis of Osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease. The pathogenesis is poorly understood. What is known is that OA is characterized by imbalance in anabolic and catabolic gene expression in articular chondrocytes.

Meta-Analysis and Evidence Base for the Efficacy of Autologous Bone Marrow Mesenchymal Stem Cells in Knee Cartilage Repair: Methodological Guidelines and Quality Assessment.

The aim of this study is to review all the published clinical trials on autologous bone marrow mesenchymal stem cells (BM-MSCs) in the repair of cartilage lesions of the knee. We performed a comprehensive search in three electronic databases: PubMed, Medline via Ovid, and Web of Science. A systematic review was conducted according to the guidelines of PRISMA protocol and the Cochrane Handbook for Systematic Reviews of Interventions.

Role of MicroRNA-141 in the Aging Musculoskeletal System: A Current Overview.

MicroRNA's are small non-coding RNAs that regulate the expression of genes by targeting the 3' UTR's of mRNA. Studies reveal that miRNAs play a pivotal role in normal musculoskeletal function such as mesenchymal stem cell differentiation, survivability and apoptosis, osteogenesis, and chondrogenesis. Changes in normal miRNA expression have been linked to a number of pathological disease processes.

Pros and cons of mouse models for studying osteoarthritis.

Osteoarthritis (OA) is one of the most common chronic conditions in the world today. It results in breakdown of cartilage in joints and causes the patient to experience intense pain and even disability. The pathophysiology of OA is not fully understood; therefore, there is currently no cure for OA.

Amino acids as signaling molecules modulating bone turnover.

Except for the essential amino acids (AAs), much of the focus on adequate dietary protein intake has been on total nitrogen and caloric intake rather than AA composition. Recent data, however, demonstrate that "amino-acid sensing" can occur through either intracellular or extracellular nutrient-sensing mechanisms. In particular, members of the class 3 G-protein coupled receptor family, like the calcium-sensing receptor are known to preferentially bind specific AAs, which then modulate receptor activation by calcium ions and thus potentially impact bone turnover.

Recent advances in hyaluronic acid based therapy for osteoarthritis.

Osteoarthritis is a debilitating disease that has increased in prevalence across the world due to the aging population. Currently, physicians use a plethora of treatment strategies to try and slow down the progression of the disease, but none have been shown to ubiquitously treat and cure the disease. One of the strategies uses the high molecular weight molecule hyaluronic acid as either an injectable or oral supplement for treatment.

Modulation of miRNAs by Vitamin C in Human Bone Marrow Stromal Cells.

MicroRNAs (miRNAs) are small (18-25 nucleotides), noncoding RNAs that have been identified as potential regulators of bone marrow stromal cell (BMSC) proliferation, differentiation, and musculoskeletal development. Vitamin C is known to play a vital role in such types of biological processes through various different mechanisms by altering mRNA expression. We hypothesized that vitamin C mediates these biological processes partially through miRNA regulation.

Emerging role of extracellular vesicles in musculoskeletal diseases.

Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a better understanding of the surface markers that characterize exosomes and microvesicles, and greater information derived from -omics approaches on the proteins, lipids, mRNAs, and microRNAs (miRNAs) transported by EVs. We have recently discovered a role for exosome-derived miRNAs in age-related bone loss and osteoarthritis, two conditions that impose a significant public health burden on the aging global population. Previous work has also revealed multiple roles for EVs and their miRNAs in muscle regeneration and congenital myopathies.

Kynurenine, a Tryptophan Metabolite That Accumulates With Age, Induces Bone Loss.

Age-dependent bone loss occurs in humans and in several animal species, including rodents. The underlying causal mechanisms are probably multifactorial, although an age-associated increase in the generation of reactive oxygen species has been frequently implicated. We previously reported that aromatic amino acids function as antioxidants, are anabolic for bone, and that they may potentially play a protective role in an aging environment.

Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis.

The pathogenesis of osteoarthritis (OA) is poorly understood, and therapeutic approaches are limited to preventing progression of the disease. Recent studies have shown that exosomes play a vital role in cell-to-cell communication, and pathogenesis of many age-related diseases. Molecular profiling of synovial fluid derived exosomal miRNAs may increase our understanding of OA progression and may lead to the discovery of novel biomarkers and therapeutic targets.

Extracellular vesicles in the pathogenesis of rheumatoid arthritis and osteoarthritis.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are both debilitating diseases that cause significant morbidity in the US population. Extracellular vesicles (EVs), including exosomes and microvesicles, are now recognized to play important roles in cell-to-cell communication by transporting various proteins, microRNAs (miRNAs), and mRNAs. EV-derived proteins and miRNAs impact cell viability and cell differentiation, and are likely to play a prominent role in the pathophysiology of both OA and RA.

Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disease affecting articular cartilage in joints, and it is a leading cause of disability in the United States. Current pharmacological treatment strategies are ineffective to prevent the OA progression; however, cellular therapies have the potential to regenerate the lost cartilage, combat cartilage degeneration, provide pain relief, and improve patient mobility. One of the most promising sources of cellular regenerative medicine is from mesenchymal stem cells (MSCs).

Stem Cell-Derived Exosomes: A Potential Alternative Therapeutic Agent in Orthopaedics.

Within the field of regenerative medicine, many have sought to use stem cells as a promising way to heal human tissue; however, in the past few years, exosomes (packaged vesicles released from cells) have shown more exciting promise. Specifically, stem cell-derived exosomes have demonstrated great ability to provide therapeutical benefits. Exosomal products can include miRNA, other genetic products, proteins, and various factors.

The crucial role of vitamin C and its transporter (SVCT2) in bone marrow stromal cell autophagy and apoptosis.

Vitamin C is an antioxidant that plays a vital role in various biological processes including bone formation. Previously, we reported that vitamin C is transported into bone marrow stromal cells (BMSCs) through the sodium dependent Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in osteogenic differentiation. Furthermore, this transporter is regulated by oxidative stress.

Oxidation of the aromatic amino acids tryptophan and tyrosine disrupts their anabolic effects on bone marrow mesenchymal stem cells.

Age-induced bone loss is associated with greater bone resorption and decreased bone formation resulting in osteoporosis and osteoporosis-related fractures. The etiology of this age-induced bone loss is not clear but has been associated with increased generation of reactive oxygen species (ROS) from leaky mitochondria. ROS are known to oxidize/damage the surrounding proteins/amino acids/enzymes and thus impair their normal function.

MicroRNAs-141 and 200a regulate the SVCT2 transporter in bone marrow stromal cells.

Vitamin C is a micro-nutrient which plays an important role in bone marrow stromal cell (BMSCs) differentiation to osteogenesis. This vitamin is transported into the BMSCs through the sodium dependent vitamin C transporter 2 (SVCT2). We previously reported that knockdown of the SVCT2 transporter decreases osteogenic differentiation.

Role of myostatin (GDF-8) signaling in the human anterior cruciate ligament.

Myostatin, also referred to as growth and differentiation factor-8 (GDF-8), is expressed in muscle tissue where it functions to suppress myoblast proliferation and myofiber hypertrophy. Recently, myostatin and its receptor, the type IIB activin receptor (ActRIIB), were detected in the leg tendons of mice, and recombinant myostatin was shown to increase cellular proliferation and the expression of type 1 collagen in primary fibroblasts from mouse tendons. We sought to determine whether myostatin and its receptor were present in human anterior cruciate ligament (ACL) tissue, and if myostatin treatment had any effect on primary ACL fibroblasts.

Effects of notchplasty and femoral tunnel position on excursion patterns of an anterior cruciate ligament graft.

Purpose: Errors in femoral tunnel placement in anterior cruciate ligament (ACL) reconstruction can cause excessive length changes in the graft during knee flexion and extension, resulting in graft elongation during the postoperative period. To improve the accuracy of tunnel placement and to avoid graft impingement, a notchplasty is commonly performed. The purpose of this study was to determine the effects of varying the position of the femoral tunnel and of performing a 2-mm notchplasty of the lateral femoral condyle and roof of the intercondylar notch on excursion patterns of a bone-patellar tendon-bone graft.

Effects of femoral tunnel placement on knee laxity and forces in an anterior cruciate ligament graft.

The purpose of this study was to measure the effects of variation in placement of the femoral tunnel upon knee laxity, graft pretension required to restore normal anterior-posterior (AP) laxity and graft forces following anterior cruciate ligament (ACL) reconstruction. Two variants in tunnel position were studied: (1) AP position along the medial border of the lateral femoral condyle (at a standard 11 o'clock notch orientation) and (2) orientation along the arc of the femoral notch (o'clock position) at a fixed distance of 6-7 mm anterior to the posterior wall. AP laxity and forces in the native ACL were measured in fresh frozen cadaveric knee specimens during passive knee flexion-extension under the following modes of tibial loading: no external tibial force, anterior tibial force, varus-valgus moment, and internal-external tibial torque.

Biomechanical effects of femoral notchplasty in anterior cruciate ligament reconstruction.

Notchplasty is frequently performed in conjunction with anterior cruciate ligament reconstruction. Bench loading tests were performed on 26 fresh-frozen knee specimens to measure excursion of a bone-patellar tendon-bone graft, anterior-posterior laxity of the knee, and graft forces before and after performing a 2-mm and a 4-mm notchplasty. The mean intraarticular pretension required to restore normal anterior-posterior laxity at 30 degrees of flexion (laxity-matched pretension level) was 27 N before notchplasty, 48 N after 2-mm notchplasty, and 65 N after 4-mm notchplasty.

The effect of anterior cruciate ligament graft rotation on knee laxity and graft tension: An in vitro biomechanical analysis.

Purpose: The purpose of this study was to determine the effects of rotating a bone-patellar tendon- bone allograft during anterior cruciate ligament reconstruction on anteroposterior (AP) knee laxity and forces developed within the graft.

Type Of Study: In vitro biomechanical study using human cadaveric knees.

Methods: Thirteen fresh-frozen knee specimens received bone-patella tendon-bone allografts that were pretensioned at 30 degrees of flexion to restore AP laxity to that of the intact knee.