TGFβ-1 and Healing of Bone Defects in Large Animal and Rabbit Models: A Systematic Review.

Long bone and craniofacial bone fractures amount to an overwhelming expenditure for patients and health care systems each year. Overall, 5-10% of all bone fractures result in some form of delayed or nonunion fractures. Nonunions occur from insufficient mechanical stabilization or a compromised wound environment lacking in vasculature and progenitor cells.

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner.

Bone is a frequent site for breast cancer metastasis. The vast majority of breast cancer-associated metastasis is osteolytic in nature, and RANKL (receptor activator for nuclear factor κB)-induced differentiation of bone marrow-derived macrophages to osteoclasts (OCLs) is a key requirement for osteolytic metastatic growth of cancer cells. In this study, we demonstrate that Myocardin-related transcription factor (MRTF) in breast cancer cells plays an important role in paracrine modulation of RANKL-induced OCL differentiation.

Chondrogenic potential of superficial versus cartilage layer cells of the temporomandibular joint condyle in photopolymerizable gelatin-based hydrogels.

The objectives of this study were to compare the chondrogenic potential of cells derived from different layers of Mandibular condyle cartilage and to gain further understanding of the impact of chondrogenic cues when embedded into a novel hydrogel scaffold (PGH, a polymer blend of poly (ethylene glycol), gelatin, and heparin) compared to a gelatin hydrogel scaffold (GEL). Cartilage layer cells (CLCs) and fibroblastic superficial layer cells (SLCs) were harvested from the mandibular condyle of boer goats obtained from a local abattoir. After expansion, cells were seeded into PGH and GEL hydrogels and cultured in chondrogenic media for 3 weeks.

Breast cancer cells promote osteoclast differentiation in an MRTF-dependent paracrine manner.

Unlabelled: Bone is a frequent site for breast cancer metastasis. The vast majority of breast cancer-associated metastasis is osteolytic in nature, and RANKL (receptor activator for nuclear factor κB)-induced differentiation of bone marrow-derived macrophages (BMDMs) to osteoclasts (OCLs) is a key requirement for osteolytic metastatic growth of cancer cells. In this study, we demonstrate that Myocardin-related transcription factor (MRTF) in breast cancer cells plays an important role in paracrine modulation of RANKL-induced osteoclast differentiation.

Aquaporin locus (12q13.12) might contribute to susceptibility of temporomandibular joint disorder associated with periodontitis.

Aquaporins (AQPs) are membrane channels that provide for transport of water and other small molecules across the lipid bilayer of cells. Their function is essential for physiologic processes such as cell volume regulation, chondrocyte hypertrophy during appendicular skeletal growth, water reabsorption in the kidney tubules, and water excretion by the salivary glands. The ten AQP isoforms show tissue specificity and are involved in different pathologies and inflammatory diseases.

Effect of the Periapical "Inflammatory Plug" on Dental Pulp Regeneration: A Histologic In Vivo Study.

Introduction: In the current study, we investigate the effect of the inflammation occupying the apical foramen-a phenomenon we refer to as "inflammatory plug"-on the regenerative potential of a root canal therapy.

Methods: We performed root canal treatment (RCT) in 12 canine root canals while aseptically instrumenting the apex to a 0.5-mm-wide foramen and obturating the canals with the following materials: collagen sponge, platelet-rich fibrin, and blood clot (no material introduced).

Hydrogel to guide chondrogenesis versus osteogenesis of mesenchymal stem cells for fabrication of cartilaginous tissues.

The ideal combination of hydrogel components for regeneration of cartilage and cartilaginous interfaces is a significant challenge because control over differentiation into multiple lineages is necessary. Stabilization of the phenotype of stem cell derived chondrocytes is needed to avoid undesired progression to terminal hypertrophy and tissue mineralization. A novel ternary blend hydrogel composed of methacrylated poly(ethylene glycol) (PEG), gelatin, and heparin (PGH) was designed to guide chondrogenesis by bone marrow derived mesenchymal stem cells (BMSCs) and maintenance of their cartilaginous phenotype.

Regenerative Potential of Various Soft Polymeric Scaffolds in the Temporomandibular Joint Condyle.

Purpose: Biodegradable polymeric scaffolds have been used for tissue engineering approaches and can be used to regenerate temporomandibular joint (TMJ) tissues. Synthetic acellular polymeric poly(glycerol sebacate) (PGS) scaffolds and natural scaffolds made from gelatin are polymeric scaffold sponges that could provide a substrate for cell infiltration and remodeling. The authors studied the regenerative potential of these 2 scaffolds in addition to a bioactive signal, magnesium (Mg), in a novel fibrocartilage defect model in the goat mandibular condylar cartilage (MCC).

Phenotype, function, and differentiation potential of human monocyte subsets.

Human monocytes have been grouped into classical (CD14++CD16-), non-classical (CD14dimCD16++), and intermediate (CD14++CD16+) subsets. Documentation of normal function and variation in this complement of subtypes, particularly their differentiation potential to dendritic cells (DC) or macrophages, remains incomplete. We therefore phenotyped monocytes from peripheral blood of healthy subjects and performed functional studies on high-speed sorted subsets.

β-adrenergic receptor control of endosomal PTH receptor signaling via Gβγ.

Cells express several G-protein-coupled receptors (GPCRs) at their surfaces, transmitting simultaneous extracellular hormonal and chemical signals into cells. A comprehensive understanding of mechanisms underlying the integrated signaling response induced by distinct GPCRs is thus required. Here we found that the β-adrenergic receptor, which induces a short cAMP response, prolongs nuclear cAMP and protein kinase A (PKA) activation by promoting endosomal cAMP production in parathyroid hormone (PTH) receptor signaling through the stimulatory action of G protein Gβγ subunits on adenylate cyclase type 2.

FRET Imaging in Three-dimensional Hydrogels.

Imaging of Förster resonance energy transfer (FRET) is a powerful tool for examining cell biology in real-time. Studies utilizing FRET commonly employ two-dimensional (2D) culture, which does not mimic the three-dimensional (3D) cellular microenvironment. A method to perform quenched emission FRET imaging using conventional widefield epifluorescence microscopy of cells within a 3D hydrogel environment is presented.

Development of a Spring-Loaded Impact Device to Deliver Injurious Mechanical Impacts to the Articular Cartilage Surface.

Objective: Traumatic impacts on the articular joint surface in vitro are known to lead to degeneration of the cartilage. The main objective of this study was to develop a spring-loaded impact device that can be used to deliver traumatic impacts of consistent magnitude and rate and to find whether impacts cause catabolic activities in articular cartilage consistent with other previously reported impact models and correlated with the development of osteoarthritic lesions. In developing the spring-loaded impactor, the operating hypothesis is that a single supraphysiologic impact to articular cartilage in vitro can affect cartilage integrity, cell viability, sulfated glycosaminoglycan and inflammatory mediator release in a dose-dependent manner.

EBP50 promotes focal adhesion turnover and vascular smooth muscle cells migration.

The ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a PDZ-containing scaffolding protein that regulates a variety of physiological functions. In the vasculature, EBP50 promotes neointima formation following arterial injury. In this study the role of EBP50 on vascular smooth muscle cell (VSMC) migration was characterized.

Characterization of tissue biomechanics and mechanical signaling in uterine leiomyoma.

Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA.

Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype.

Introduction: Mesenchymal stem cells (MSCs) offer promise for intervertebral disc (IVD) repair and regeneration because they are easily isolated and expanded, and can differentiate into several mesenchymal tissues. Notochordal (NC) cells contribute to IVD development, incorporate into the nucleus pulposus (NP), and stimulate mature disc cells. However, there have been no studies investigating the effects of NC cells on adult stem cell differentiation.

Experimental and computational characterization of designed and fabricated 50:50 PLGA porous scaffolds for human trabecular bone applications.

The present study utilizes image-based computational methods and indirect solid freeform fabrication (SFF) technique to design and fabricate porous scaffolds, and then computationally estimates their elastic modulus and yield stress with experimental validation. 50:50 Poly (lactide-co-glycolide acid) (50:50 PLGA) porous scaffolds were designed using an image-based design technique, fabricated using indirect SFF technique, and characterized using micro-computed tomography (micro-CT) and mechanical testing. Micro-CT data was further used to non-destructively predict the scaffold elastic moduli and yield stress using a voxel-based finite element (FE) method, a technique that could find application in eventual scaffold quality control.

Human mesenchymal stem cells express vascular cell phenotypes upon interaction with endothelial cell matrix.

Mesenchymal stem cells (MSCs) are thought to occupy a perivascular niche where they are exposed to signals originating from vascular cells. This study focused on the effects of endothelial cell (EC)-derived signals on MSC differentiation toward vascular cell lineages. Upon co-culture with two types of ECs, macrovascular (macro) ECs and microvascular (micro) ECs, the former caused MSCs to increase expression of both EC and smooth muscle cell (SMC) markers, while the latter induced expression of EC markers only.

Mesenchymal stem cell modification of endothelial matrix regulates their vascular differentiation.

Mesenchymal stem cells (MSCs) respond to a variety of differentiation signal provided by their local environments. A large portion of these signals originate from the extracellular matrix (ECM). At the same time, MSCs secrete various matrix-altering agents, including proteases, that alter ECM-encoded differentiation signals.

Engineered osteochondral grafts using biphasic composite solid free-form fabricated scaffolds.

Tissue engineering has provided an alternative to traditional strategies to repair cartilage damaged by injury or degenerative disease. A successful strategy to engineer osteochondral tissue will mimic the natural contour of the articulating surface, achieve native mechanical properties and functional load-bearing ability, and lead to integration with host cartilage and underlying subchondral bone. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match articular geometry.

Earliest mineral and matrix changes in force-induced musculoskeletal disease as revealed by Raman microspectroscopic imaging.

Unlabelled: Craniosynostosis, premature fusion of the skull bones at the sutures, is the second most common human birth defect in the skull. Raman microspectroscopy was used to examine the composition, relative amounts, and locations of the mineral and matrix produced in mouse skulls undergoing force-induced craniosynostosis. Raman imaging revealed decreased relative mineral content in skulls undergoing craniosynostosis compared with unloaded specimens.

Skeletal homeostasis in tissue-engineered bone.

Tissue-engineering strategies to stimulate bone regeneration may offer an alternative approach to conventional orthopaedic and maxillofacial surgical therapies. Over the last decade, significant advances have been accomplished in developing biomimetic matrices, growth factors, cell transplantation and gene delivery therapeutics to support new bone growth. However, it is not known if tissue-engineered bone recapitulates the biology of normal skeletal tissue in response to physiologic cues.