Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway.

Introduction: In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ).

Postoperative outcomes and trends in computer-navigated and robotic-assisted total hip arthroplasty.

Introduction: As the volume of technology-assisted total hip arthroplasty (THA) increases, there is a need to characterise the outcomes of robotic-assisted (RA) and computer-navigated (CN) THA. The goal of this study was to assess outcomes and opioid consumption following CN-THA and RA-THA compared to conventionally-instrumented (CON) THA.

Methods: The Premier Database was queried for all patients who underwent primary, elective THA from 2015-2020.

Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling.

The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone.

Tumor Promoters and Opportunities for Molecular Cancer Prevention.

Environmental carcinogens increase cancer incidence via both mutagenic and non-mutagenic mechanisms. There are over 500 known or suspected carcinogens classified by the International Agency for Research on Cancer. Sequencing of both cancerous and histologically non-cancerous tissue has been instrumental in improving our understanding of how environmental carcinogens cause cancer.

Differential Responses to Aging Among the Transcriptome and Proteome of Mesenchymal Progenitor Populations.

The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in 3 different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues.

The Role of Aryl Hydrocarbon Receptor in Bone Biology.

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is crucial in maintaining the skeletal system. Our study focuses on encapsulating the role of AhR in bone biology and identifying novel signaling pathways in musculoskeletal pathologies using the GEO dataset. The GEO2R analysis identified 8 genes (CYP1C1, SULT6B1, CYB5A, EDN1, CXCR4B, CTGFA, TIPARP, and CXXC5A) involved in the AhR pathway, which play a pivotal role in bone remodeling.

Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.

The biological aging of mesenchymal stem cells is proposed to contribute to the development of a range of musculoskeletal and systemic diseases associated with older adults, such as osteoporosis, sarcopenia, and frailty. Despite this, little is understood about the specific mechanisms which drive this stem cell exhaustion, with most studies evaluating indirect effects of other aging changes, such as DNA damage, senescence, and inflammaging. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues.

The Intersection of Race and Sex: A New Perspective Into Diversity Trends in Orthopaedic Surgery.

Introduction: Studies on diversity in orthopaedic surgery have exclusively examined challenges from a race or sex perspective. This study examines trends in the diversity of entering orthopaedic surgery residents from the intersection of race and sex.

Methods: The American Association of Medical Colleges was queried for individuals entering orthopaedic surgery residencies in the United States from 2001 to 2020.

Circulating Osteoprogenitor Cells Have a Mixed Immune and Mesenchymal Progenitor Function in Humans.

Background: Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. However, a comprehensive functional characterization of COP cells is still required to test and fully develop their use in clinical settings.

Identifying Factors of Operative Efficiency in Head and Neck Free Flap Reconstruction.

Importance: Head and neck oncological resection and reconstruction is a complex process that requires multidisciplinary collaboration and prolonged operative time. Numerous factors are associated with operative time, including a surgeon's experience, team familiarity, and the use of new technologies. It is paramount to evaluate the contribution of these factors and modalities on operative time to facilitate broad adoption of the most effective modalities and reduce complications associated with prolonged operative time.

Knee Extensor Mechanism Complications After Autograft Harvest in ACL Reconstruction: A Systematic Review and Meta-analysis.

Background: Existing systematic reviews have sought to characterize the relative donor-site morbidity of bone-patellar tendon-bone (BTB) and quadriceps tendon (QT) grafts after anterior cruciate ligament reconstruction (ACLR). However, no studies have reported the pooled proportions of patellar fractures and donor tendon ruptures across the body of literature.

Purpose: To estimate the proportion of patellar fractures, patellar tendon ruptures, and QT ruptures associated with BTB or QT autograft harvest during ACLR using published data.

Orchiectomy sensitizes cortical bone in male mice to the harmful effects of kynurenine.

Kynurenine (Kyn) is a tryptophan metabolite that increases with age and promotes musculoskeletal dysfunction. We previously found a sexually dimorphic pattern in how Kyn affects bone, with harmful effects more prevalent in females than males. This raises the possibility that male sex steroids might exert a protective effect that blunts the effects of Kyn in males.

Inhibiting MicroRNA-141-3p Improves Musculoskeletal Health in Aged Mice.

Emerging evidence shows that the microRNA-141-3p is involved in various age-related pathologies. Previously, our group and others reported elevated levels of miR-141-3p in several tissues and organs with age. Here, we inhibited the expression of miR-141-3p using antagomir (Anti-miR-141-3p) in aged mice and explored its role in healthy aging.

Trends in Race and Sex Representation Among Entering Orthopaedic Surgery Residents: A Continued Call for Active Diversification Efforts.

Introduction: Multiple studies have analyzed the diversity of surgical subspecialties, in which orthopaedic surgery consistently lags behind in female and minority representation. This study aims to examine contemporary data on trends in sex and racial representation among entering orthopaedic surgery residents.

Methods: The American Association of Medical Colleges' Graduate Medical Education Track data set was queried for all individuals entering surgical residencies in the United States from 2001 to 2020.

Lung adenocarcinoma promotion by air pollutants.

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development. Here we propose that environmental particulate matter measuring ≤2.

DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence.

Bone marrow skeletal stem cells (SSCs) secrete many cytokines including stromal derived factor-1 or CXCL12, which influences cell proliferation, migration, and differentiation. All CXCL12 splice variants are rapidly truncated on their N-terminus by dipeptidyl peptidase 4 (DPP4). This includes the common variant CXCL12 alpha (1-68) releasing a much less studied metabolite CXCL12(3-68).

Upregulation of the EGFR/MEK1/MAPK1/2 signaling axis as a mechanism of resistance to antiestrogen‑induced BimEL dependent apoptosis in ER breast cancer cells.

The epidermal growth factor receptor (EGFR) is commonly upregulated in multiple cancer types, including breast cancer. In the present study, evidence is provided in support of the premise that upregulation of the EGFR/MEK1/MAPK1/2 signaling axis during antiestrogen treatment facilitates the escape of breast cancer cells from BimEL‑dependent apoptosis, conferring resistance to therapy. This conclusion is based on the findings that ectopic BimEL cDNA overexpression and confocal imaging studies confirm the pro‑apoptotic role of BimEL in ERα expressing breast cancer cells and that upregulated EGFR/MEK1/MAPK1/2 signaling blocks BimEL pro‑apoptotic action in an antiestrogen‑resistant breast cancer cell model.

Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice.

Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver signaling axis contributes to gut microbiota effects on bone.

Alterations in bone metabolites with age in C57BL/6 mice model.

Understanding the pathophysiology behind age-related diseases is an urgent need as the elderly population continues to grow. With age, there is a high risk of musculoskeletal deterioration and associated morbidity and mortality. Although the exact mechanism behind age-related degeneration is unknown, it is well established that alteration in cellular metabolism is one of the important contributing factors.

Aryl hydrocarbon receptor (AhR)-mediated signaling as a critical regulator of skeletal cell biology.

The aryl hydrocarbon receptor (AhR) has been implicated in regulating skeletal progenitor cells and the activity of bone-forming osteoblasts and bone-resorbing osteoclasts, thereby impacting bone mass and the risk of skeletal fractures. The AhR also plays an important role in the immune system within the skeletal niche and in the differentiation of mesenchymal stem cells into other cell lineages including chondrocytes and adipocytes. This transcription factor responds to environmental pollutants which can act as AhR ligands, initiating or interfering with various signaling cascades to mediate downstream effects, and also responds to endogenous ligands including tryptophan metabolites.

Computer-Navigated and Robotic-Assisted Total Knee Arthroplasty: Increasing in Popularity Without Increasing Complications.

Background: Data on the clinical impact of computer navigation (CN) and robotic assistance (RA) in total knee arthroplasty (TKA) are mixed. This study aims to describe modern utilization trends in CN-TKA, RA-TKA, and traditionally-instrumented (TD) TKA and to assess for differences in postoperative complications and opioid consumption by procedure type.

Methods: A national database was queried to identify primary, elective TKA patients from 2015 to 2020.

Long Non-coding RNA MALAT1 Is Depleted With Age in Skeletal Muscle and MALAT1 Silencing Increases Expression of TGF-β1 .

Long non-coding RNAs (lncRNAs) are thought to function as "sponges" for microRNAs, but a role for such competing endogenous RNAs (ceRNAs) in muscle aging is not well understood. We therefore examined in skeletal muscles of young (4-6 months) and aged (22-24) male and female mice the expression of lncRNA MALAT1, which is predicted to bind the senescence-associated microRNA miR-34a-5p. Results indicate a significant decrease in lncRNA MALAT1 expression in mouse skeletal muscle with age that coincides with an age-related increase in miR-34a-5p expression.

Accounting for dimensional differences in stochastic domain invasion with applications to precancerous cell removal.

We consider a specific form of domain invasion that is an abstraction of pancreatic tissue eliminating precancerous mutant cells through juxtacrine signalling. The model is explored discretely, continuously, stochastically and deterministically, highlighting unforeseen nonlinear dependencies on the dimension of the solution domain. Specifically, stochastically simulated populations invade with a dimension dependent wave speed that can be over twice as fast as their deterministic analogues.