Abstract The success of cell-based therapies to restore joint cartilage requires an optimal source reparative progenitor cells and tight control their differentiation into a permanent phenotype. Bone morphogenetic protein 2 (BMP-2) has been extensively shown promote mesenchymal cell chondrocytes in vitro vivo. Conversely, developmental studies have demonstrated decreased chondrocyte maturation by Wingless-Type MMTV Integration Site Family, Member 5A (Wnt5a). Thus, we hypothesized that...

Preclinical animal study.Determine the in vivo effects of platelet-derived growth factor BB (PDGF-BB) delivered a thiol-modified hyaluronic acid (TMHA) hydrogel on intervertebral disk (IVD) degeneration.IVD degeneration is worldwide health concern and remains without an effective treatment. Several vitro studies have demonstrated potential PDGF-BB, primary component platelet-rich plasma, as therapy for IVD degeneration. Our hypotheses were that treatment injured IVDs with PDGF would inhibit...

In the United States, over 17 million people are diagnosed with type 1 diabetes mellitus (DM) its inherent morbidity of delayed bone healing and nonunion. Recent studies demonstrate utility pulsed low-intensity ultrasound (LIPUS) to facilitate fracture healing. The current study evaluated effects daily application LIPUS on mid-diaphyseal femoral growth factor expression, cartilage formation, neovascularization in DM non-DM BB Wistar rats. Polymerase chain reaction (PCR) ELISA assays were...

Fifteen patients have shown neovascularity in the left heart during selective coronary arteriography, with associated fistulous communication to a cardiac chamber ten. In nine abnormalities were adjacent and within ventricular mural thrombi, aneurysms seven congestive cardiomyopathy two. six mitral stenosis atrial fibrillation angiographic changes related thrombi. Histologic study of two thrombi showed revascularization patterns keeping both findings an intermediate stage evolution thrombus....

Abstract Local insulin delivery has been shown to improve osseous healing in diabetic animals. The purpose of this study was quantify the effects local intramedullary saline or Ultralente (UL) on various fracture parameters using an vivo non‐diabetic BB Wistar rat model. Quantitation levels showed a rapid release from fractured femora, demonstrating complete at 2 days. RT‐PCR analysis revealed that expression early osteogenic markers (Col1α2, osteopontin) significantly enhanced with UL...

Degeneration of the intervertebral disc (IVD) results in deterioration spinal motion segment and can lead to debilitating back pain. Given established mitotic anti-apoptotic effects recombinant human platelet-derived growth factor-BB (rhPDGF-BB) a variety cell types we postulated that rhPDGF-BB might delay degeneration through inhibition apoptosis. To address this hypothesis, treated IVD cells isolated from five independent patients with monolayer 3D pellet cultures. The potential,...

Each year, over one million orthopedic operations are performed which a bony defect is presence, requiring the use of further augmentation in addition to fixation. Application autogenous bone graft standard care promote healing these defects, but several determents exist using including limited supply and donor site morbidity. Prior work has demonstrated that local insulin application fracture sites healing, no been date its effects upon healing/allograft incorporation. The goal this study...

Abstract This study quantified the effects of local intramedullary delivery an organic vanadium salt, which may act as insulin‐mimetic on fracture healing. Using a BB Wistar rat femoral model, vanadyl acetylacetonate (VAC) was delivered to site and histomorphometry, mechanical testing, immunohistochemistry were performed. Callus percent cartilage 200% higher at day 7 ( p < 0.05) 88% 10 in animals treated with 1.5 mg/kg VAC. mineralized tissue 37% 14 31% 21 Maximum torque failure 104% 154%...

This study investigated the effects of local delivery manganese chloride (MnCl2), an insulin-mimetic compound, upon fracture healing using a rat femoral model. Mechanical testing, histomorphometry, and immunohistochemistry were performed to assess early late parameters healing. At 4 weeks post-fracture, maximum torque failure was 70% higher (P<0.05) torsional rigidity increased 133% in animals treated with 0.125 mg/kg MnCl2 compared saline controls. Histological analysis callus revealed...

ABSTRACT This study evaluated the effect of local zinc chloride (ZnCl 2 ), an insulin mimetic agent, upon early and late parameters fracture healing in rats using a standard femur model. Mechanical testing, radiographic scoring, histomorphometry, qualitative histological PCNA immunohistochemistry, growth factor analysis were performed. Fractures treated with ZnCl possessed significantly increased mechanical properties compared to controls at 4 weeks post fracture. The scoring showed cortical...

Abstract Bone remodeling is achieved through the coupled activities of osteoclasts and osteoblasts that are controlled by many locally generated secreted factors, including WNT5A. While previous studies have demonstrated osteoblast‐derived WNT5A promotes osteoclastogenesis, function osteoclast‐derived on bone has remained unexplored. We examined effects homeostasis utilizing Cathepsin K ‐ Cre ( Ctsk ) mouse to conditionally delete Wnt5a in mature osteoclasts. These mice exhibited reduced...

Abstract A significant number of lower extremity fractures result in mal‐union necessitating effective treatments to restore ambulation. Prior research diabetic animal fracture models demonstrated improved healing following local insulin application the site and indicated that therapy can aid bone regeneration, at least within an insulin‐dependent model. This study tested whether could accelerate femur repair normal, non‐diabetic rats. High (20 units) low (10 doses were delivered a calcium...

Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype CD11b-Cre Runx1fl/fl mice and demonstrated enhanced osteoclasts decreased mass males. However, an assessment effects Runx1 deletion female osteoclast precursors was impossible with this model. Moreover, role myeloid cell differentiation into other lineages unknown. Therefore, generated LysM-Cre mice, which delete equally (∼80% deletion)...

ABSTRACT This study evaluated the efficacy of using calcium sulfate (CaSO 4 ) as a carrier for intramedullary delivery an organic vanadium salt, vanadyl acetylacetonate (VAC) after femoral fracture. VAC can act insulin‐mimetic and be used to accelerate fracture healing in rats. A heterogenous mixture CaSO was delivered site BB Wistar rats, mechanical testing, histomorphometry, micro‐computed tomography (micro‐CT) were performed measure healing. At weeks fracture, maximum torque failure,...

Osteoarthritis (OA) is a degenerative disease and major cause of chronic disability in aging individuals. Cathepsin K (CatK), encoded by the Ctsk gene, has been implicated pathogenesis pycnodysostosis osteoporosis. The use selective inhibitor CatK was recently shown to delay OA progression rabbits. However, cellular mechanisms underlying these protective effects remain unexplored. We examined articular cartilage maintenance joint bone remodeling using null mice ( ‐/‐ ) which underwent...

Conditional deletion of the transcription factor Runt-related 1 (Runx1) in myeloid osteoclast precursors promotes osteoclastogenesis and subsequent bone loss. This study posits whether Runx1 regulates clastic cell-mediated cartilage resorption fracture callus. We first generated mice, which was conditionally abrogated (LysM-Cre;Runx1F/F ; cKO). cKO control mice were then subjected to experimental mid-diaphyseal femoral fractures. Our found differential bony calcified callus matrix by...

Keratinocytes produce a variety of cytokines, including leukemia inhibitory factor. We hypothesised that this cytokine may play pro-inflammatory role in the skin and tested hypothesis by injecting recombinant factor (1-100 ng) into ear pinnae C3H/HeJ mice. To other groups animals, we injected boiled or phosphate-buffered saline (negative control) 0.4 ng human interleukin-1 alpha as positive control. Following injection 100 factor, thickness, measured micrometer, increased 66% over controls...

Abstract The effects of naproxen, a nonsteroidal anti‐inflammatory drug (NSAID), on articular cartilage degeneration in female Sprague–Dawley rats was examined. Osteoarthritis (OA) induced by destabilization the medial meniscus (DMM) each knee. Rats were treated with acetaminophen (60 mg/kg), naproxen (8 or 1% carboxymethylcellulose (placebo) oral gavage twice daily for 3 weeks, beginning 2 weeks after surgery. OA severity assessed histological Research Society International (OARSI) scoring...

Background The purpose of this study was to quantify the levels growth factors (platelet-derived factor [PDGF] AB, vascular endothelial [VEGF], insulin-like [IFG] 1, and transforming [TGF]- β1) within bone samples at fusion site diabetic patients undergoing hindfoot arthrodesis determine any correlation with successful fusion. Methods included 10 adult from one US center, an average age 57.9 years (range 49–71 years). Interventions arthrodeses a fixator (n=8) pantalar (n=2). During each...

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis patients with diminished healing capabilities, such as individuals type 1 diabetes mellitus (T1DM) who have impaired capabilities and increased risk of developing osteoporosis. This study measured the effects rhBMP-2 treatment on by observing dose-dependent effect localized delivery biomechanical parameters using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier T1DM-related...

The bHLH transcription factor Twist1 has emerged as a negative regulator of chondrogenesis in skeletal progenitor cells and an inhibitor maturation growth plate chondrocytes. However, its role articular cartilage remains obscure. Here we examine expression during re-differentiation expanded human chondrocytes, the distribution proteins normal versus OA cartilage, modulating development mice. High levels transcripts were detected by qPCR analyses de-differentiated chondrocytes that had...

The multifaceted sequence of events that follow fracture repair can be further complicated when considering risk factors for impaired union, present in a large and growing percentage the population. Risk such as diabetes, substance abuse, poor nutrition affect both young old alike, have been shown to dramatically impair body's natural healing processes. To this end, biotherapeudic interventions ultrasound, electrical simulation, growth factor treatment (BMP-2, BMP-7, PDGF-BB, FGF-2)...

Objectives: Wnt5a expression is upregulated during fracture repair and has previously been implicated as a potential regulator of skeletal development bone mass accrual maintenance. Our objective was to evaluate the function in healing. Methods: Femoral experiments on Wnt5a+/+ Wnt5a+/− mice were carried out. To better understand effect repair, we evaluated radiographs using validated qualitative scoring system performed microcomputed tomography analyses. Histomorphometric analyses determined...