Image-seq: spatially resolved single-cell sequencing guided by in situ and in vivo imaging.

Tissue function depends on cellular organization. While the properties of individual cells are increasingly being deciphered using powerful single-cell sequencing technologies, understanding their spatial organization and temporal evolution remains a major challenge. Here, we present Image-seq, a technology that provides single-cell transcriptional data on cells that are isolated from specific spatial locations under image guidance, thus preserving the spatial information of the target cells.

Dendritic cell-specific transmembrane protein is required for synovitis and bone resorption in inflammatory arthritis.

Objective: Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is essential for the formation of fully functional multinucleated osteoclasts. DC-STAMP deficient mice, under physiological conditions, exhibit osteopetrosis and develop systemic autoimmunity with age. However, the function of DC-STAMP in inflammation is currently unknown.

Defining the spatial-molecular map of fibrotic tendon healing and the drivers of Scleraxis-lineage cell fate and function.

Tendon injuries heal via a scar-mediated response, and there are no biological approaches to promote more regenerative healing. Mouse flexor tendons heal through the formation of spatially distinct tissue areas: a highly aligned tissue bridge between the native tendon stubs that is enriched for adult Scleraxis-lineage cells and a disorganized outer shell associated with peri-tendinous scar formation. However, the specific molecular programs that underpin these spatially distinct tissue profiles are poorly defined.

Bone Metastases of Diverse Primary Origin Frequently Express the VDR (Vitamin D Receptor) and CYP24A1.

Active vitamin D (1,25(OH)2D3) is known to exert direct anti-cancer actions on various malignant tissues through binding to the vitamin D receptor (VDR). These effects have been demonstrated in breast, prostate, renal and thyroid cancers, which all have a high propensity to metastasise to bone. In addition, there is evidence that vitamin D catabolism via 24-hydroxylase (CYP24A1) is altered in tumour cells, thus, reducing local active vitamin D levels in cancer cells.

Chondrogenic Differentiation of Human-Induced Pluripotent Stem Cells.

The generation of large quantities of genetically defined human chondrocytes remains a critical step for the development of tissue engineering strategies for cartilage regeneration and high-throughput drug screening. This protocol describes chondrogenic differentiation of human-induced pluripotent stem cells (hiPSCs), which can undergo genetic modification and the capacity for extensive cell expansion. The hiPSCs are differentiated in a stepwise manner in monolayer through the mesodermal lineage for 12 days using defined growth factors and small molecules.

Radiographic Parameters in Cervical Myelopathy: Review of Current Literature.

Study Design: This was a narrative review.

Objectives: Provide a comprehensive review of radiographic alignment parameters and their effect on procedure selection, surgical decision-making, and clinical outcomes for the treatment of cervical spondylotic myelopathy (CSM).

Summary Of Background Data: The use of radiographic parameters to predict prognosis and surgical outcomes in patients with CSM is an evolving field given the complex presentation of patients with this condition.

High-resolution imaging of the osteogenic and angiogenic interface at the site of murine cranial bone defect repair via multiphoton microscopy.

The spatiotemporal blood vessel formation and specification at the osteogenic and angiogenic interface of murine cranial bone defect repair were examined utilizing a high-resolution multiphoton-based imaging platform in conjunction with advanced optical techniques that allow interrogation of the oxygen microenvironment and cellular energy metabolism in living animals. Our study demonstrates the dynamic changes of vessel types, that is, arterial, venous, and capillary vessel networks at the superior and dura periosteum of cranial bone defect, suggesting a differential coupling of the vessel type with osteoblast expansion and bone tissue deposition/remodeling during repair. Employing transgenic reporter mouse models that label distinct types of vessels at the site of repair, we further show that oxygen distributions in capillary vessels at the healing site are heterogeneous as well as time- and location-dependent.

Identification of Penicillin Binding Protein 4 (PBP4) Inhibitors.

Methicillin-resistant (MRSA) is a global healthcare concern. Such resistance has historically been attributed to the acquisition of (or ), which encodes an alternative penicillin binding protein, PBP2a, with low β-lactam affinity. However, recent studies have indicated that penicillin binding protein 4 (PBP4) is also a critical determinant of methicillin resistance, particularly among community-acquired MRSA strains.

Fracture-related infection.

Musculoskeletal trauma leading to broken and damaged bones and soft tissues can be a life-threating event. Modern orthopaedic trauma surgery, combined with innovation in medical devices, allows many severe injuries to be rapidly repaired and to eventually heal. Unfortunately, one of the persisting complications is fracture-related infection (FRI).

Skeletal interoception in bone homeostasis and pain.

Accumulating evidence indicates that interoception maintains proper physiological status and orchestrates metabolic homeostasis by regulating feeding behaviors, glucose balance, and lipid metabolism. Continuous skeletal remodeling consumes a tremendous amount of energy to provide skeletal scaffolding, support muscle movement, store vital minerals, and maintain a niche for hematopoiesis, which are processes that also contribute to overall metabolic balance. Although skeletal innervation has been described for centuries, recent work has shown that skeletal metabolism is tightly regulated by the nervous system and that skeletal interoception regulates bone homeostasis.

The Impact of the COVID-19 Pandemic on the Presentation of Patients With Spinal Metastases.

Study Design: Retrospective review.

Objective: The aim was to determine if preoperative spinal instability neoplastic scores (SINSs) and Tokuhashi prognostication scores differed in patients receiving surgical care before and during the coronavirus disease-2019 (COVID-19) pandemic.

Summary Of Background Data: The COVID-19 pandemic has caused delays in scheduling nonemergent surgeries.

CCR2 is expressed by tendon resident macrophage and T cells, while CCR2 deficiency impairs tendon healing via blunted involvement of tendon-resident and circulating monocytes/macrophages.

During tendon healing, macrophages are thought to be a key mediator of scar tissue formation, which prevents successful functional restoration of the tendon. However, macrophages are critical for successful tendon healing as they aid in wound debridement, extracellular matrix deposition, and promote fibroblast proliferation. Recent work has sought to better define the multi-faceted functions of macrophages using depletion studies, while other studies have identified a tendon resident macrophage population.

Assessing the Insurance Deductible Effect on Outcomes After Elective Spinal Surgery.

Background: Private insurers use the calendar deductible system, placing pressure on patients and medical personnel to perform medical services before the end of the year to maximize patient savings. The impact of the deductible calendar on patient-reported outcomes (PROs) after spine surgery is poorly understood. The objective of our study was to investigate if patients undergoing surgery in December had different PROs and demographics compared with all other months.

Technology-Enhanced Delivery Models to Facilitate the Implementation of Psychologically Informed Practice for Chronic Musculoskeletal Pain.

Chronic musculoskeletal pain is prevalent, challenging to treat, and often disabling. Evidence supports the role of psychological factors in pain-related outcomes, and it is now accepted that rehabilitation should combine physical and psychological approaches (ie, psychologically informed practice). This Perspective articulates a vision for technology-enhanced psychologically informed practice for chronic musculoskeletal pain, highlights relevant research evidence, discusses how technology can circumvent implementation barriers, and proposes directions for future research.

The Ideal Threshold of Hemoglobin A1C in Diabetic Patients Undergoing Elective Lumbar Decompression Surgery.

Study Design: Retrospective cohort study.

Objective: To evaluate the association of Hemoglobin A1C (HbA1c) with surgical site infection (SSI) and patient-reported outcomes (PROs), and to identify optimal HbA1c thresholds to minimize the risk of SSI and maximize PROs.

Summary Of Background Data: Diabetes mellitus has been associated with worsened outcomes following spine surgery.

Craniofacial tendon development-Characterization of extracellular matrix morphology and spatiotemporal protein distribution.

Craniofacial (CF) tendons are often affected by traumatic injuries and painful disorders that can severely compromise critical jaw functions, such as mastication and talking. Unfortunately, tendons lack the ability to regenerate, and there are no solutions to restore their native properties or function. An understanding of jaw tendon development could inform tendon regeneration strategies to restore jaw function, however CF tendon development has been relatively unexplored.

Current understanding of osteoarthritis pathogenesis and relevant new approaches.

Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body. The molecular mechanisms of OA are currently unknown. OA is a heterogeneous disease that affects the entire joint, and multiple tissues are altered during OA development.

Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts.

Extracellular sulfatase-2 (Sulf-2) influences receptor-ligand binding and subsequent signaling by chemokines and growth factors, yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis (RA). In the present study, we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts (RASFs). Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg mice.

Dual peptide-functionalized hydrogels differentially control periodontal cell function and promote tissue regeneration.

Restoring the tooth-supporting tissues lost during periodontitis is a significant clinical challenge, despite advances in both biomaterial and cell-based approaches. This study investigated poly(ethylene glycol) (PEG) hydrogels functionalized with integrin-binding peptides RGD and GFOGER for controlling periodontal ligament cell (PDLC) activity and promoting periodontal tissue regeneration. Dual presentation of RGD and GFOGER within PEG hydrogels potentiated two key PDLC functions, alkaline phosphatase (ALP) activity and matrix mineralization, over either peptide alone and could be tuned to differentially promote each function.

HSP expression depends on its molecular construction and different organs of the chicken: a meta-analysis.

Heat shock proteins (HSPs) expression protect the cell from stress, this expression varies on tissue and stress level. Here, we investigated the structure and functional expression of HSPs in different chicken organs using meta-analysis. A total of 1253 studies were collected from three different electronic databases from January 1, 2015 to February 1, 2022.

Are Surgeons' Tendencies to Avoid Discomfort Associated with Attitudes and Beliefs Toward Patient Psychosocial Factors?

Background: Orthopedic surgeons are sometimes hesitant to assess and address psychosocial factors. Surgeon-specific modifiable factors may contribute to surgeon attitudes and beliefs regarding the mental and social aspects of illness. A better understanding of these factors could help inform interventions to support surgeons and improve patient outcomes.

Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation.

Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial, and its role in patients with S. aureus osteomyelitis is unknown. To address this knowledge gap, we completed a clinical study and observed elevated serum IL-27 levels (20-fold higher, P < 0.

Tendon mechanical properties are enhanced recombinant lysyl oxidase treatment.

Tendon mechanical properties are significantly compromised in adult tendon injuries, tendon-related birth defects, and connective tissue disorders. Unfortunately, there currently is no effective treatment to restore native tendon mechanical properties after postnatal tendon injury or abnormal fetal development. Approaches to promote crosslinking of extracellular matrix components in tendon have been proposed to enhance insufficient mechanical properties of fibrotic tendon after healing.