Revealing a Natural Model of Pre-Osteoarthritis of the Hip Through Study of Femoroacetabular Impingement.

Femoroacetabular impingement (FAI) is considered the mechanical cause of hip osteoarthritis (OA). Surgical intervention involves labrum repair and osteochondroplasty to remove the impingement, alleviating symptoms. Nevertheless, some patients progress to hip OA after surgery, indicating that factors other than mechanical abnormality are contributing to hip OA progression.

PROMIS Physical Function and Pain Interference Scores Correlate with the Lower Extremity Toronto Extremity Salvage Score.

Unlabelled: The Toronto Extremity Salvage Score (TESS) and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) are both utilized to measure patient-reported outcomes in adults with musculoskeletal oncologic conditions. However, the relationship between them has not been studied. We sought to describe a link between Lower Extremity (LE) TESS and PROMIS Physical Function (PF) scores, as well as between LE TESS and Pain Interference (PI) scores, to develop a method for converting scores between TESS and PROMIS and to examine whether TESS and PROMIS captured differences in pain and function between clinically relevant subgroups in our population.

Did the Physical and Mental Health of Orthopaedic Patients Change After the Onset of the COVID-19 Pandemic?

Background: The 2019 novel coronavirus (COVID-19) pandemic has been associated with poor mental health outcomes and widened health disparities in the United States. Given the inter-relationship between psychosocial factors and functional outcomes in orthopaedic surgery, it is important that we understand whether patients presenting for musculoskeletal care during the pandemic were associated with worse physical and mental health than before the pandemic's onset.

Questions/purposes: (1) Did patients seen for an initial visit by an orthopaedic provider during the COVID-19 pandemic demonstrate worse physical function, pain interference, depression, and/or anxiety than patients seen before the pandemic, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) instrument? (2) During the COVID-19 pandemic, did patients living in areas with high levels of social deprivation demonstrate worse patterns of physical function, pain interference, depression, or anxiety on initial presentation to an orthopaedic provider than patients living in areas with low levels of social deprivation, compared with prepandemic PROMIS scores?

Methods: This was a retrospective, comparative study of new patient evaluations that occurred in the orthopaedic department at a large, urban tertiary care academic medical center.

Epigenetic dysregulation of articular cartilage during progression of hip femoroacetabular impingement disease.

Femoroacetabular impingement (FAI) is an important trigger of hip osteoarthritis (OA). Epigenetic changes in DNA methyltransferase 3B (DNMT3B) attenuate catabolic gene expression in cartilage hemostasis. This study aimed to examine the articular chondrocyte catabolic state and DNMT3B and 4-aminobutyrate aminotransferase promoter (ABAT) expression during OA progression in FAI.

Patients With Metastatic Disease Are at Highest Risk for Anxiety and Depression in an Orthopedic Oncology Patient Population.

Purpose: Patients with cancer are at risk for anxiety and depression; however, the patterns and predictors of symptoms in an orthopedic oncology population have not been studied.

Methods: We retrospectively reviewed Patient-Reported Outcomes Measurement Information System scores of all adult patients who underwent palliative surgery for metastatic cancer, resection of a sarcoma, or nononcologic total joint arthroplasty at a single institution from 2015 to 2020. Backward stepwise linear regression was used to determine risk factors for perioperative anxiety and depression.

Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102.

Purpose: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis.

Experimental Design: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings.

A Novel Model of Hip Femoroacetabular Impingement in Immature Rabbits Reproduces the Distinctive Head-Neck Cam Deformity.

Background: Femoroacetabular impingement (FAI) is a leading cause of hip pain in young adults and often leads to degenerative osteoarthritis (OA). A small animal model of hip deformities is crucial for unraveling the pathophysiology of hip OA secondary to FAI.

Purposes: To (1) characterize a new minimally invasive surgical technique to create a proximal femoral head-neck deformity in a skeletally immature rabbit model and (2) document the effect of an injury to the medial proximal femoral epiphysis on head-neck morphology at 28 days after the injury.

Otto Aufranc Award: Identification of Key Molecular Players in the Progression of Hip Osteoarthritis Through Transcriptomes and Epigenetics.

Background: This study aimed: (1) to compare the transcriptome profile of articular cartilage in cam-FAI (early stage) to advanced OA secondary to cam-FAI (late stage) and (2) to investigate epigenetic changes through the expression of DNA methylation enzymes DNMT3B, DNMT1, and DNMT3A and peroxisome proliferator-activated receptor gamma (PPARγ) in human cartilage samples during the progression of hip OA.

Methods: Full-thickness cartilage samples were collected from the anterolateral head-neck junction (impingement zone) of 22 patients (9 early-FAI and 13 late-FAI). RNA sequencing and in vitro cartilage cultures with histological analysis and immunohistochemistry staining for PPARγ and DNMT3B were performed.

Deletion of Glut1 in early postnatal cartilage reprograms chondrocytes toward enhanced glutamine oxidation.

Glucose metabolism is fundamental for the functions of all tissues, including cartilage. Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development, little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis. We show here that genetic deletion of the glucose transporter Glut1 in postnatal cartilage impairs cell proliferation and matrix production in growth plate (GPs) but paradoxically increases cartilage remnants in the metaphysis, resulting in shortening of long bones.

FoxO1 is a crucial mediator of TGF-β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis.

Transforming growth factor-β (TGF-β) signaling is a critical regulator for articular cartilage tissue maintenance and chondrocyte homeostasis. Nonetheless, the regulatory networks and downstream signaling pathways that govern the chondroprotective function of TGF-β in the context of osteoarthritis (OA) are not fully defined. Recent studies reveal that mice with postnatal deletion of triple forkhead box class Os (FoxOs) (1, 3, and 4) spontaneously develop OA-like pathologies.

Isolation and Culture of Periosteum-Derived Progenitor Cells from Mice.

This chapter describes the methods of isolation of mouse periosteal progenitor cells. There are three basic methods utilized. The bone grafting method was developed utilizing the fracture healing process to expand the progenitor populations.

Runx2 plays a central role in Osteoarthritis development.

Unlabelled: Osteoarthritis (OA) is the most common form of arthritis, is the leading cause of impaired mobility in the elderly, and accounts for more than a third of chronic moderate to severe pain. As a degenerative joint disorder, OA affects the whole joint and results in synovial hyperplasia, degradation of articular cartilage, subchondral sclerosis, osteophyte formation, and chronic pain. Currently, there is no effective drug to decelerate OA progression and molecular targets for drug development have been insufficiently investigated.

Distinct Pattern of Inflammation of Articular Cartilage and the Synovium in Early and Late Hip Femoroacetabular Impingement.

Background: The molecular mechanism of how femoroacetabular impingement (FAI) morphology leads to hip osteoarthritis (OA) is yet to be determined. The expression and location of inflammation-related molecules during early- and late-stage FAI have not been previously described. Moreover, the characterization of intra-articular inflammation away from the cam deformity as well as the nature of adjacent synovial tissue have also not been extensively reported.

LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis.

The contribution of inflammation to the chronic joint disease osteoarthritis (OA) is unclear, and this lack of clarity is detrimental to efforts to identify therapeutic targets. Here we show that chondrocytes under inflammatory conditions undergo a metabolic shift that is regulated by NF-κB activation, leading to reprogramming of cell metabolism towards glycolysis and lactate dehydrogenase A (LDHA). Inflammation and metabolism can reciprocally modulate each other to regulate cartilage degradation.

Inflammatory Response of Articular Cartilage to Femoroacetabular Impingement in the Hip.

Background: Femoroacetabular impingement (FAI) has been proposed as an etiologic factor in up to 50% of hips with osteoarthritis (OA). Inflammation is thought to be one of the main initiators of OA, yet little is known about the origin of intra-articular inflammation in FAI hips.

Hypothesis: Articular cartilage from the impingement zone of patients with FAI has high levels of inflammation, reflecting initial inflammatory process in the hip.

Dnmt3b ablation impairs fracture repair through upregulation of Notch pathway.

We previously established that DNA methyltransferase 3b (Dnmt3b) is the sole Dnmt responsive to fracture repair and that Dnmt3b expression is induced in progenitor cells during fracture repair. In the current study, we confirmed that Dnmt3b ablation in mesenchymal progenitor cells (MPCs) resulted in impaired endochondral ossification, delayed fracture repair, and reduced mechanical strength of the newly formed bone in Prx1-Cre;Dnmt3bf/f (Dnmt3bPrx1) mice. Mechanistically, deletion of Dnmt3b in MPCs led to reduced chondrogenic and osteogenic differentiation in vitro.

American Society for Bone and Mineral Research-Orthopaedic Research Society Joint Task Force Report on Cell-Based Therapies - Secondary Publication.

Cell-based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell-based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web-based marketing and patient testimonials supporting cell-based therapy.

Patient-Reported Outcomes Measurement Information System physical function correlates with Toronto Extremity Salvage Score in an orthopaedic oncology population.

Background: The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) uses computerised-adaptive testing to reduce survey burden and improve sensitivity. PROMIS is being used across medical and surgical disciplines but has not been studied in orthopaedic oncology.

Questions/purposes: The aim of the study was to compare PROMIS measures with upper extremity (UE) and lower extremity (LE) Toronto Extremity Salvage Score (TESS) by assessing the following: (1) responder burden, (2) correlation between scores and (3) floor/ceiling effects.

American Society for Bone and Mineral Research-Orthopaedic Research Society Joint Task Force Report on Cell-Based Therapies.

Cell-based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell-based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web-based marketing and patient testimonials supporting cell-based therapy.