Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research.

Cite this article: Bone Joint J 2019;101-B:361–364.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases.

Cite this article: J. Zhang, X. Hao, M. Yin, T. Xu, F. Guo. Long non-coding RNA in osteogenesis: A new world to be explored. Bone Joint Res 2019;8:73–80. DOI: 10.1302/2046-3758.82.BJR-2018-0074.R1.

The aim of this randomised, controlled in vivo study in an ovine model was to investigate the effect of cylic pneumatic pressure on fracture healing. We performed a transverse osteotomy of the right radius in 37 sheep. They were randomised to a control group or a treatment group where they received cyclic loading of the osteotomy by the application of a pressure cuff around the muscles of the proximal forelimb. Sheep from both groups were killed at four or six weeks. Radiography, ultrasonography, biomechanical testing and histomorphometry were used to assess the differences between the groups. The area of periosteal callus, peak torsional strength, fracture stiffness, energy absorbed over the first 10° of torsion and histomorphometric analysis all showed that the osteotomies treated with the cyclic pneumatic pressure at four weeks were not significantly different from the control osteotomies at six weeks

Our purpose was to determine the mechanism which allows the maximum knee flexion in vivo after a posterior-cruciate-ligament (PCL)-retaining total knee arthroplasty. Using three-dimensional computer-aided design videofluoroscopy of deep squatting in 29 patients, we determined that in 72% of knees, direct impingement of the tibial insert posteriorly against the back of the femur was the factor responsible for blocking further flexion. In view of this finding we defined a new parameter termed the ‘posterior condylar offset’. In 150 consecutive arthroplasties of the knee, the magnitude of posterior condylar offset was found to correlate with the final range of flexion

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth

We analysed the axis of movement in the normal elbow during flexion in vivo using radiostereometric analysis (RSA). The results show an intraindividual variation in the inclination of the axis ranging from 2.1° to 14.3° in the frontal and from 1.6° to 9.8° in the horizontal plane analysed at 30° increments. The inclination of the mean axis of rotation varied within a range of 12.7° in the frontal and 4.6° in the horizontal plane. In both planes, the mean axes were located close to a line joining the centres of the trochlea and capitellum. The intra- and interindividual variations of the axes of flexion of the elbow were greater than previously reported. These factors should be considered in the development of elbow prostheses

1. A method is described for the in vivo and in vitro study of osteogenesis by implanting a modified transparent chamber in half lop-eared rabbits (as originated by Sandison 1928). This method allows the daily observation and photography of the developing bone and the study of its intimate connection with the vascularity of the area. 2. The osteogenetic potential of a variety of substances can also be investigated by this method. The tissue in the chamber can easily be prepared for its final examination by optical and electron microscopy and by other laboratory techniques

Aims

The aim of this study was to evaluate the surface damage, the density of crosslinking, and oxidation in retrieved antioxidant-stabilized highly crosslinked polyethylene (A-XLPE) tibial inserts from total knee arthroplasty (TKA), and to compare the results with a matched cohort of standard remelted highly crosslinked polyethylene (XLPE) inserts.

Objectives

The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known.

The study describes the topography, morphology and growth of osteophytes in forty femoral heads removed from patients presenting with advanced osteoarthritis of the hip. In addition to standard histological techniques, radiography of serial bone slices and in vivo bone labelling with tetracycline and . 32. P were used. The pattern of major osteophyte formation appeared to be influenced by the direction, degree and rate of displacement of the femoral head in relation to the acetabulum; four principal patterns of growth were noted. Osteophytes form part of extensive osteogenic processes that involve bone structure in the osteoarthritic joint

Objectives

Prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty. Non-contact induction heating of metal implants is a new and emerging treatment for PJI. However, there may be concerns for potential tissue necrosis. It is thought that segmental induction heating can be used to control the thermal dose and to limit collateral thermal injury to the bone and surrounding tissues. The purpose of this study was to determine the thermal dose, for commonly used metal implants in orthopaedic surgery, at various distances from the heating centre (HC).

The complete removal of the cement mantle at revision arthroplasty can be extremely difficult. Some authors advise a ‘cement-within-cement’ revision technique in which a new layer of cement is applied to the old before insertion of the femoral component. We could find no long-term clinical data regarding the success of this procedure. In a simple biomechanical study, we examined the strength of the cement-to-cement interface in conditions likely to prevail in vivo. We found that the presence of a thin layer of blood and marrow debris at the interface weakened the cement-to-cement bond by 80% to 85%. These biomechanical findings and additional photomicrographic evidence do not support the practice of cement-within-cement revision arthroplasty

Objectives

Many in vitro studies have investigated the mechanism by which mechanical signals are transduced into biological signals that regulate bone homeostasis via periodontal ligament fibroblasts during orthodontic treatment, but the results have not been systematically reviewed. This review aims to do this, considering the parameters of various in vitro mechanical loading approaches and their effects on osteogenic and osteoclastogenic properties of periodontal ligament fibroblasts.

We report two cases of surface deterioration of a zirconia ceramic femoral head associated with phase transformation after total hip arthroplasty. One head was retrieved at revision due to recurrent dislocation after six years and the other because of failure of the locking mechanism of the polyethylene liner after three years. The monoclinic content of the zirconia ceramics rose from 1% to about 30% on the surface of the heads. SEM revealed numerous craters indicating extraction of the zirconia ceramics at the surface. Surface roughness increased from an initial value of 0.006 3m up to 0.12 3m. This is the first report to show that phase transformation of zirconia ceramics causes deterioration of the surface roughness of the head in vivo after total hip arthroplasty

Objectives

Unicompartmental knee arthroplasty (UKA) is one surgical option for treating symptomatic medial osteoarthritis. Clinical studies have shown the functional benefits of UKA; however, the optimal alignment of the tibial component is still debated. The purpose of this study was to evaluate the effects of tibial coronal and sagittal plane alignment in UKA on knee kinematics and cruciate ligament tension, using a musculoskeletal computer simulation.

We used 99 strains of organisms representative of orthopaedic infections to examine the effectiveness of a bone cement containing tobramycin, employing a modified in vitro Kirby-Bauer susceptibility model. The spectrum was broad, including Gram-positive and Gram-negative aerobic organisms, anaerobes and mycobacteria. Simplex P with added tobramycin was effective against most of the strains, including those which are resistant to typical systemic levels of tobramycin. Although direct correlation between in vitro and in vivo results is difficult, the study showed that tobramycin is stable to the exothermic polymerisation of the cement, and that it is released from the surface of the cement at concentrations high enough to inhibit the growth of most organisms which may be encountered after joint arthroplasty

1. Bone changes in the haemoglobinopathies are caused by either (a) chronic haemolysis with marrow hyperplasia, or (b) infarction, when Hb S is present in the red cells in amounts sufficient to allow sickling (and therefore vascular occlusion) in vivo. 2. Marrow hyperplasia produces osteoporosis, widening of the medulla, and thinning of the cortex; it may lead to spontaneous fractures and disturbances of growth. Enlargement of the foramina of the nutrient arteries may be seen especially in the phalanges. Infarcts leading to aseptic necrosis occur in the long bones, and may become infected with Salmonella organisms. The range of radiological lesions caused by these processes is illustrated

1. The utilisation of radioactive sulphur in vivo has been demonstrated both macroscopically and microscopically during the preosseous stage of bone repair. 2. The labelled mucopolysaccharide complex, chondroitin sulphuric acid, has been studied during the formation of the medullary and periosteal blastemata in the healing of a fracture. 3. The appearance and possible significance of mast cells adjacent to a fracture, and resulting from the stimulus of trauma, are discussed. 4. Cortisone has been seen to affect the formation of the periosteal cartilaginous blastema and subsequent process of endochondral ossification, with liberation of increased amounts of chondroitin sulphuric acid which was calcified rather than ossified

Aims

Early implant migration measured with radiostereometric analysis (RSA) has been proposed as a useful predictor of long-term fixation of tibial components in total knee arthroplasty. Evaluation of actual long-term fixation is of interest for cemented components, as well as for cementless fixation, which may offer long-term advantages once osseointegration has occurred. The objective of this study was to compare the long-term migration with one- and two-year migration to evaluate the predictive ability of short-term migration data and to compare migration and inducible displacement between cemented and cementless (porous metal monoblock) components at least ten years postoperatively.