Cigarette smoking has a negative impact on the
Advances in our understanding of
Recent approaches have sought to harness the potential of stem cells to regenerate bone lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the
Introduction and Objective. Calcium phosphates are among the most commonly used bone graft substitute materials. Compositions containing predominantly monetite (∼84.7%) with smaller additions of beta-tricalcium phosphate (β-TCP; ∼8.3%) and calcium pyrophosphate (Ca-PP; ∼6.8%) have previously been demonstrated to exhibit osteoinductive properties. Such a multi-component calcium phosphate bioceramic was fashioned in the form of hollowed-out, dome-shaped devices (15 mm diameter, 4 mm height), each reinforced with a 3D printed Ti6Al4V ELI frame. With the aim to induce bone formation beyond the
Tissue engineering is a promising approach to regenerate damaged
TGF-beta signaling has a well established role not only in adult organ homeostasis but also in
Osteoporosis affects millions globally and current anti-catabolic treatments are limited by significant side-effects. Osteoporosis arises when
Osteoarthritis is characterised by the loss and damage of cartilage in synovial joints. Whilst joint replacement is the gold standard for end stage disease, repair or regenerative strategies aim to slow disease progression, maintain joint function and defer the need for joint replacement. One approach seeks to target endogenous repair after drilling or microfracture (a type of trauma induced repair) in the area of cartilage loss – connecting the defect to the underlying bone marrow niche. The rationale of this approach is that cells delivered to the defect site, from the bone marrow, will bring about cartilage repair. Bone marrow contains multipotent cells, including stem and stromal populations, of both the haematopoietic and
Osteoporosis (OP) and osteoarthritis (OA) are leading causes of musculoskeletal dysfunction in elderly, with chondrocyte senescence, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability as prominent features. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Not surprisingly, the development of OP and OA correlate with dysregulations of the gut microflora in rodents and humans. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis, autophagy, and redox reactions in chondrocytes to regulate joint homeostasis. Modulating the abundance of specific gut bacteria, like Lactobacillus and Bifidobacterium, by probiotics or fecal microbiota transplantation appears to suppress age-induced chronic inflammation and oxidative damage in musculoskeletal tissue and holds potential to slow down OP development. The talk will highlight treatment options with probiotics or metabolites for modulating the progression of OA and OP.
Objectives. Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine. Methods. Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs). Results. The supernatant contained several GFs/CKs, with especially high levels of basic fibroblast growth factor, and CD34+ cells as the stem/progenitor cell fraction. With regard to biological potential, we confirmed that cell proliferation, osteoinduction, and angiogenesis in hMSCs and HUVECs were enhanced by the supernatant. Conclusions. The current study demonstrates the potential of a new point-of-care strategy for regenerative medicine using skeletal muscle supernatant. This attractive approach and readily-available material could be a promising option for tissue repair/regeneration in the clinical setting. Cite this article: M. Yoshikawa, T. Nakasa, M. Ishikawa, N. Adachi, M. Ochi. Evaluation of autologous
Bone tissue experiences continued remodelling in response to changes in its biochemical and biophysical environment. Given the finite lifespan of osteoblasts, this continued bone formation requires replenishment from a progenitor population. Although this is largely believed to be from a
Background. Following endosteal uncemented orthopaedic device implantation, the initial implant/bone interface retains spaces and deficiencies further exacerbated by pressure necrosis and resultant bone resorption. This implant-bone space requires native bone infill through the process of de novo osteogenesis. New appositional bone formation on the implant surface is known as contact osteogenesis and is generated by osteogenic cells, including
Angiogenesis and the ability to provide appropriate vascular supply are crucial for
AIM. Avascular necrosis (AVN) of the femoral head is a potentially debilitating disease of the hip in young adults. Impaction bone grafting (IBG) of morcellised fresh frozen allograft is used in a number of orthopaedic conditions. This study has examined the potential of
Introduction. The proteoglycan aggrecan is a major component of the cartilaginous matrices which provides resistance against compressive forces. Spontaneously occurring functional null mutations in the aggrecan gene (Acan) in various species lead to perinatal chondrodysplasia. The aim of the present study was to investigate the cellular and biomechanical properties of the cartilaginous growth plate, and the development of intervertebral disc in a novel, experimentally induced aggrecan mutant mouse strain carrying an insertion in exon 5 of the Acan gene. Methods. The novel aggrecan mutant mice were generated by inserting a loxP site into exon 5 (E5i) by homologous recombination in ES cells. Wild type and homozygous mutant (Acan-E5i/E5i) mice were analyzed by
Background. Metastatic bone patients who require surgery needs to be evaluated in order to maximise quality of life and avoiding functional impairment, minimising the risks connected to the surgical procedures. The best surgical procedure needs to be tailored on survival estimation. There are no current available tool or method to evaluate survival estimation with accuracy in patients with bone metastasis. We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable
Background. Lengthening over nail (LON) and the use of internal lengthening nails have been developed to minimize patients' time in a frame during femur lengthening. This study compares the outcomes of two techniques of femur lengthening, LON and Intramedullary
Osteoporosis (OP) results in a reduction in the mechanical competence of the bone tissue of the sufferers. In
With around 20–40% of our bodyweight, skeletal muscles are the biggest organ complex of the human body. Being a metabolic active tissue, muscle mass, function and fibertype composition is highly regulated in a tight spatial-temporal manner. In geriatric patients, it is essentially important to understand the underlying mechanisms of the age related losses of fiber size and total number of fibers, as well as fibertype shifting. To date, there have been few studies dealing with gene expression profiling of skeletal muscles, mostly focusing on age related differences in whole-muscle specimen. Being carried out on mouse or rat limb muscles, most other studies do not represent the conditions of human muscle, due to the differences in fibertype composition. Our study provides a fibertype-specific approach for whole-genome expression analysis in human skeletal muscle. 22 fresh frozen biceps brachii and quadriceps femoris muscle samples were acquired from the muscle bank of the Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-University, Munich, Germany. Consecutive cross-sections were used for immunohistochemical myosine-heavy-chain-staining and individual fibers were acquired by laser-capture-microdissection. Around 100 cells of each fibertype of each biopsy were dissected, reversely transcribed, pre-amplified and labeled for microarray analysis. Fiber type-specific gene expression was analyzed with ANOVA. Correction for multiple testing was performed using the Benjamini-Hochberg procedure with a conservative threshold and the pathway analysis was carried out using the Ingenuity Pathway Analysis program (QIAGEN). By comparing type I vs. type IIa, type I vs. type IIx and type IIa vs. type IIx, we could identify 2855, 2865 and 510 differentially expressed genes. As expected, many differentially regulated genes belong to functional groups like cytoskeleton, muscle contraction and energy metabolism, proving the feasibility of our study. However, many genes that are involved in the response to oxidative stress were also differently regulated, showing distinct mechanisms of the different fiber types, of coping with oxidative stress. In consensus with available literature, the relative proportion of type I fibers seemed to increase with age. Despite higher levels of oxidative stress, type I fibers seem to have more efficient antioxidative mechanisms in comparison to type IIa and IIx fibers, which might explain the higher vulnerability of members of the type II family to oxidative stress. Furthermore, genes that are involved in fibertype specification were also regulated differently. However, we could not verify an age-specific activation of pathways involved in fibertype shifting. Whether fibertype shifting is solely due to disproportionate loss of type II fibers, or also in vivo - transdifferentiation of fibers, has to be investigated further.