Novel In Vitro Platform for Studying the Cell Response to Healthy and Diseased Tendon Matrices.

Current in vitro models poorly represent the healthy or diseased tendon microenvironment, limiting the translation of the findings to clinics. The present work aims to establish a physiologically relevant in vitro tendon platform that mimics biophysical aspects of a healthy and tendinopathic tendon matrix using a decellularized bovine tendon and to characterize tendon cells cultured using this platform. Bovine tendons were subjected to various decellularization techniques, with the efficacy of decellularization determined histologically.

Factors secreted by monosodium urate crystal-stimulated macrophages promote a proinflammatory state in osteoblasts: a potential indirect mechanism of bone erosion in gout.

Background: Tophi are lesions commonly present at sites of bone erosion in gout-affected joints. The tophus comprises a core of monosodium urate (MSU) crystals surrounded by soft tissue that contains macrophages and other immune cells. Previous studies found that MSU crystals directly reduce osteoblast viability and function.

Basic calcium phosphate crystals induce the expression of extracellular matrix remodelling enzymes in tenocytes.

Objectives: Basic calcium phosphate (BCP) crystals contribute to several syndromes associated with tendon disease, including acute calcific tendinitis and Milwaukee shoulder syndrome. Interactions between BCP crystals and tenocytes (tendon cells) may contribute to these clinical syndromes. This study aimed to determine the direct effects of BCP crystals on tenocyte function and viability.

Changes in Physiological Tendon Substrate Stiffness Have Moderate Effects on Tendon-Derived Cell Growth and Immune Cell Activation.

Tendinopathy is characterised by pathological changes in tendon matrix composition, architecture, and stiffness, alterations in tendon resident cell characteristics, and fibrosis, with inflammation also emerging as an important factor in tendinopathy progression. The sequence of pathological changes in tendinopathy and the cellular effects of the deteriorating matrix are largely unknown. This study investigated the effects of substrate stiffness on tendon-derived cells (TDCs) and THP-1 macrophages using PDMS substrates representing physiological tendon stiffness (1.

Age-related differences in hamstring tendon used as autograft in reconstructive anterior cruciate ligament surgery.

Purpose: The hamstring tendon is the most commonly used autograft material in reconstructive surgeries of anterior cruciate ligament (ACL) tears. Younger patients have worse surgical outcomes, with a higher risk of re-rupture. We hypothesized that age-related changes in hamstring tendon properties affect the tendon's propensity to rupture when used as an autograft in ACL reconstructions.

Molecular characterisation of osteoblasts from bone obtained from people of Polynesian and European ancestry undergoing joint replacement surgery.

Population studies in Aotearoa New Zealand found higher bone mineral density and lower rate of hip fracture in people of Polynesian ancestry compared to Europeans. We hypothesised that differences in osteoblast proliferation and differentiation contribute to the differences in bone properties between the two groups. Osteoblasts were cultured from bone samples obtained from 30 people of Polynesian ancestry and 25 Europeans who had joint replacement surgeries for osteoarthritis.

Raman spectroscopy reveals age- and sex-related differences in cortical bone from people with osteoarthritis.

Bone strength in human cortical bone is determined by the composition and structure of both the mineral and collagen matrices and influenced by factors such as age, gender, health, lifestyle and genetic factors. Age-related changes in the bone matrix are known to result in loss of mechanical strength and increased fragility. In this study we show how Raman spectroscopy, with its exquisite sensitivity to the molecular structure of bone, reveals new insights into age- and sex-related differences.

The effect of age on the microarchitecture and profile of gene expression in femoral head and neck bone from patients with osteoarthritis.

Ageing of the skeleton is characterised by decreased bone mineral density, reduced strength, and increased risk of fracture. Although it is known that these changes are determined by the activities of bone cells through the processes of bone modelling and remodelling, details of the molecular mechanisms that underlie age-related changes in bone are still missing. Here, we analysed age-related changes in bone microarchitecture along with global gene expression in samples obtained from patients with osteoarthritis (OA).

HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA: A NOVEL HOMOZYGOUS MUTATION IN AND LITERATURE REVIEW.

Objective: Hypophosphatemic rickets with hypercalciuria (HHRH) is a rare, recessively-inherited form of rickets caused by homozygous or compound heterozygous mutations in the gene that encodes the renal tubular phosphate transporter protein NaPi2c. The bone phenotype varies from severe rickets to no disease. Accurate diagnosis is important as the treatment differs from other forms of rickets.

Design, characterization and evaluation of β-hairpin peptide hydrogels as a support for osteoblast cell growth and bovine lactoferrin delivery.

The use of peptide hydrogels is of growing interest in bone regeneration. Self-assembling peptides form hydrogels and can be used as injectable drug delivery matrices. Injected into the defect site, they can gel , and release factors that aid bone growth.

Epidemiology of tendon and ligament injuries in Aotearoa/New Zealand between 2010 and 2016.

Background: Injuries to tendons and ligaments make up a large portion of musculoskeletal injuries, and contribute to significant morbidity and healthcare costs. However, there is currently a poor understanding of the burden of these injuries at a population level. The purpose of this study was to quantify the burden and distribution of tendon and ligament injuries in the Aotearoa/New Zealand population.

Juvenile Paget's disease with compound heterozygous mutations in TNFRSF11B presenting with recurrent clavicular fractures and a mild skeletal phenotype.

Juvenile Paget's disease (JPD) is a rare recessively-inherited bone dysplasia. The great majority of cases described to date have had homozygous mutations in TNFRSF11B, the gene encoding osteoprotegerin. We describe a boy who presented with recurrent clavicular fractures following minor trauma (8 fractures from age 2 to 11).

Bone-Bound Bisphosphonates Inhibit Proliferation of Breast Cancer Cells.

Bisphosphonates are used in treating patients with breast cancer. In vitro studies have shown that bisphosphonates act directly on tumour cells, inhibiting cell proliferation and inducing apoptosis. In most such studies, drugs were added to culture media exposing cells to high bisphosphonate concentrations in solution.

Bovine bone particulates containing bone anabolic factors as a potential xenogenic bone graft substitute.

Background: Alternative grafts are needed to improve the healing of bone non-union. Here, we assessed a bovine bone product which retains the inorganic and organic components of bone, as an alternative bone graft.

Methods: Bovine bone matrix proteins (BBMPs) were isolated from bovine bone particulates (BBPs) and tested in vitro.

The Activity of Peptides of the Calcitonin Family in Bone.

Calcitonin was discovered over 50 yr ago as a new hormone that rapidly lowers circulating calcium levels. This effect is caused by the inhibition of calcium efflux from bone, as calcitonin is a potent inhibitor of bone resorption. Calcitonin has been in clinical use for conditions of accelerated bone turnover, including Paget's disease and osteoporosis; although in recent years, with the development of drugs that are more potent inhibitors of bone resorption, its use has declined.

Monosodium urate crystals reduce osteocyte viability and indirectly promote a shift in osteocyte function towards a proinflammatory and proresorptive state.

Background: Bone erosion is a frequent complication of gout and is strongly associated with tophi, which are lesions comprising inflammatory cells surrounding collections of monosodium urate (MSU) crystals. Osteocytes are important cellular mediators of bone remodeling. The aim of this study was to investigate the direct effects of MSU crystals and indirect effects of MSU crystal-induced inflammation on osteocytes.

Differentiation of osteoclast precursors on gellan gum-based spongy-like hydrogels for bone tissue engineering.

Bone tissue engineering with cell-scaffold constructs has been attracting a lot of attention, in particular as a tool for the efficient guiding of new tissue formation. However, the majority of the current strategies used to evaluate novel biomaterials focus on osteoblasts and bone formation, while osteoclasts are often overlooked. Consequently, there is limited knowledge on the interaction between osteoclasts and biomaterials.

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes , but PDGF may be.

Introduction: Recently, bone-active factors such as parathyroid hormone and lactoferrin, have been used in pre-clinical models to promote tendon healing. How-ever, there is limited understanding of how these boneactive factors may affect the cells of the ten-don themselves. Here, we present an in vitro study assessing the effects of parathyroid hor-mone and lactoferrin on primary tendon cells (tenocytes), and compare their responses to the tenogenic factors, PDGF, IGF-1 and TGF-β.

Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A Laboratory and Clinical Study.

Introduction: Numerous observational studies have reported that serum urate concentration positively correlates with bone density and reduced risk of fractures. The aim of this study was to examine whether soluble urate directly influences bone remodelling.

Methods: In laboratory studies, the in vitro effects of soluble urate were examined in osteoclast, osteoblast and osteocyte assays at a range of urate concentrations consistent with those typically observed in humans (up to 0.

Human Spinal Bone Dust as a Potential Local Autograft: In Vitro Potent Anabolic Effect on Human Osteoblasts.

Study Design: In vitro Study.

Objective: To evaluate the effect that factors released from human posterior spinal bone dust have on primary human osteoblast growth and maturation.

Summary Of Background Data: Bone dust, created during spinal fusion surgeries, has the potential to be used as an autologous bone graft by providing a source of viable autologous osteoblasts and mesenchymal stem cells with osteogenic potential.

Induction of immune gene expression and inflammatory mediator release by commonly used surgical suture materials: an experimental in vitro study.

Background: Surgeons have a range of materials to choose from to complete wound closure, yet surprisingly very little is still known about the body's immune response to the suture materials in current use. The growing literature of adverse suture material reactions provided the objective of this study, to use in vitro assays to quantify levels of inflammation produced by seven commonly used suture materials in surgical procedures.

Methods: Human monocyte/macrophage THP-1 cells were exposed to suture materials for 1, 3 and 5 days.

Cell-cell communication in bone development and whole-body homeostasis and pharmacological avenues for bone disorders.

Cell-cell communication plays a crucial role in bone development and maintenance, in health and disease. Our knowledge of the signalling pathways that regulate the communication of osteoblasts, osteoclasts and osteocytes is improving with time, giving us a better understanding of the regulation of the bone remodelling process. Bone cell communication has wider significance than the local tissue environment, however, with bone derived factors playing a role in whole-body homeostasis, including energy metabolism and kidney function.

The Activity of Adiponectin in Bone.

The adipokine adiponectin affects multiple target tissues and plays important roles in glucose metabolism and whole-body energy homeostasis. Circulating adiponectin levels in obese people are lower than in non-obese, and increased serum adiponectin is associated with weight loss. Numerous clinical studies have established that fat mass is positively related to bone mass, a relationship that is maintained by communication between the two tissues through hormones and cytokines.

Local application of lactoferrin promotes bone regeneration in a rat critical-sized calvarial defect model as demonstrated by micro-CT and histological analysis.

Lactoferrin is a multifunctional glycoprotein with therapeutic potential for bone tissue engineering. The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five-millimetre critical-sized defects were created over the right parietal bone in 64 Sprague-Dawley rats.

Tyrosine Kinase Inhibitors Regulate OPG through Inhibition of PDGFRβ.

Nilotinib and imatinib are tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). In vitro, imatinib and nilotinib inhibit osteoclastogenesis, and in patients they reduce levels of bone resorption. One of the mechanisms that might underlie these effects is an increase in the production of osteoprotegerin (OPG).