One of the aims of this work was to find criteria by which the quality of bone as a supporting tissue might be judged. This inevitably involves discussion and, if possible, assessment, of the relative importance of the inorganic and organic material of the bone. It is relatively easy to measure the mineral content, and for that reason it has always received more than its due share of attention. In the present experiment the composition of the ash of all bones was remarkably constant, with a Ca/P ratio of 2. Furthermore, X-ray crystallography showed that the structure of the inorganic material was the same in all cases. The great difficulty of measuring variations in the quality of the organic material which is, of course, protein in nature makes it impossible to say how much it influences bone strength. Since at least 40 per cent. of the bone is
Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies.Aims
Methods
1. A clinical, radiological and histological description of a patient with fibrogenesis imperfecta ossium is given. We think that this is the first case in which diagnosis has been made during the life of the patient. 2. The disease is characterised by a defect in the formation of the
1. A description is given of the pathology of a generalised skeletal disease characterised by a defect in the formation of the
To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up. We reviewed 155 patients (155 knees) who underwent MOHTO from January 2008 to December 2016 followed by second-look arthroscopy with a mean 5.3-year follow-up (2.0 to 11.7). Arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. Patients were divided into two groups based on the presence of normal or nearly normal quality cartilage in the medial femoral condyle: good (second-look arthroscopic) status (ICRS grade I or II; n = 70), and poor (second-look arthroscopic) status (ICRS grade III or IV; n = 85) groups at the time of second-look arthroscopy. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-Item Short Form survey.Aims
Methods
Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect. A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus.Aims
Methods
Bone-ACL-bone allograft transplantation is a potential solution to the problem of reconstruction of the anterior cruciate ligament (ACL), but sterilisation by gamma irradiation or ethylene oxide causes degradation of the graft. We have studied the biomechanical and histological properties of deep-frozen canine bone-ACL-bone allografts sterilised by gamma irradiation (2.5 Mrad) under argon gas protection. Particular attention was paid to their
Biochemical markers of bone-turnover have long been used to complement the radiological assessment of patients with metabolic bone disease. Their implementation in daily clinical practice has been helpful in the understanding of the pathogenesis of osteoporosis, the selection of the optimal dose and the understanding of the progression of the onset and resolution of treatment. Since they are derived from both cortical and trabecular bone, they reflect the metabolic activity of the entire skeleton rather than that of individual cells or the process of mineralisation. Quantitative changes in skeletal-turnover can be assessed easily and non-invasively by the measurement of bone-turnover markers. They are commonly subdivided into three categories; 1) bone-resorption markers, 2) osteoclast regulatory proteins and 3) bone-formation markers. Because of the rapidly accumulating new knowledge of bone matrix biochemistry, attempts have been made to use them in the interpretation and characterisation of various stages of the healing of fractures. Early knowledge of the individual progress of a fracture could help to avoid delayed or nonunion by enabling modification of the host’s biological response. The levels of bone-turnover markers vary throughout the course of fracture repair with their rates of change being dependent on the size of the fracture and the time that it will take to heal. However, their short-term biological variability, the relatively low bone specificity exerted, given that the production and destruction of
We examined the mechanical properties of Vicryl (polyglactin 910) mesh in vitro and assessed its use in vivo as a novel biomaterial to attach tendon to a hydroxyapatite-coated metal implant, the interface of which was augmented with autogenous bone and marrow graft. This was compared with tendon re-attachment using a compressive clamp device in an identical animal model. Two- and four-ply sleeves of Vicryl mesh tested to failure under tension reached 5.13% and 28.35% of the normal ovine patellar tendon, respectively. Four-ply sleeves supported gait in an ovine model with 67.05% weight-bearing through the operated limb at 12 weeks, without evidence of mechanical failure. Mesh fibres were visible at six weeks but had been completely resorbed by 12 weeks, with no evidence of chronic inflammation. The tendon-implant neoenthesis was predominantly an indirect type, with tendon attached to the bone-hydroxyapatite surface by perforating
The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors. Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes. There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and
To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors.Aims
Methods
We used an in vivo model to assess the use of an autogenous cancellous bone block and marrow graft for augmenting tendon reattachment to metallic implants. We hypothesised that augmentation of the tendon-implant interface with a bone block would enable retention of the graft on the implant surface, enhance biological integration, and result in more consistent functional outcomes compared with previously reported morcellised graft augmentation techniques. A significant improvement in functional weight-bearing was observed between six and 12 weeks. The significant increase in ground reaction force through the operated limb between six and 12 weeks was greater than that reported previously with morcellised graft augmented reconstructions. Histological appearance and
The aim of this study was to evaluate the cultivation potential of cartilage taken from the debrided edge of a chronic lesion of the articular surface. A total of 14 patients underwent arthroscopy of the knee for a chronic lesion on the femoral condyles or trochlea. In addition to the routine cartilage biopsy, a second biopsy of cartilage was taken from the edge of the lesion. The cells isolated from both sources underwent parallel cultivation as monolayer and three-dimensional (3D) alginate culture. The cell yield, viability, capacity for proliferation, morphology and the expressions of typical cartilage genes (collagen I, COL1;
Objectives. This study aimed to investigate time-dependent gene expression
of injured human anterior cruciate ligament (ACL), and to evaluate
the histological changes of the ACL remnant in terms of cellular
characterisation. Methods. Injured human ACL tissues were harvested from 105 patients undergoing
primary ACL reconstruction and divided into four phases based on
the period from injury to surgery. Phase I was <
three weeks,
phase II was three to eight weeks, phase III was eight to 20 weeks,
and phase IV was ≥ 21 weeks. Gene expressions of these tissues were
analysed in each phase by quantitative real-time polymerase chain
reaction using selected markers (collagen types 1 and 3, biglycan,
decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1).
Immunohistochemical staining was also performed using primary antibodies
against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3). . Results. Expression of IL-6 was mainly seen in phases I, II and III, collagen
type 1 in phase II, MMP-1, 2 in phase III, and decorin, TGF-β1 and α-smooth
muscle actin in phase IV. Histologically, degradation and scar formation
were seen in the ACL remnant after phase III. The numbers of CD55
and P-Stat3 positive cells were elevated from phase II to phase
III. . Conclusions. Elevated cell numbers including P-Stat3 positive cells were not
related to
LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action.Aims
Methods
The primary aim of this study was to assess if traumatic triangular fibrocartilage complex (TFCC) tears can be treated successfully with immobilization alone. Our secondary aims were to identify clinical factors that may predict a poor prognosis. This was a retrospective analysis of 89 wrists in 88 patients between January 2015 and January 2019. All patients were managed conservatively initially with either a short-arm or above-elbow custom-moulded thermoplastic splint for six weeks. Outcome measures recorded included a visual analogue scale for pain, Patient-Rated Wrist Evaluation, Disabilities of the Arm, Shoulder and Hand score, and the modified Mayo Wrist Score (MMWS). Patients were considered to have had a poor outcome if their final MMWS was less than 80 points, or if they required eventual surgical intervention. Univariate and logistic regression analyses were used to identify independent predictors for a poor outcome.Aims
Methods
1. The fibrillar networks of adult human articular cartilage, taken from femoral and acetabular specimens, have been systematically examined by scanning electron microscopy. The internal structures revealed by rupturing the tissue were compared with published findings from transmission electron microscope studies. 2. Though this technique demonstrated the internal fibrillar appearance of cartilage to a remarkable degree, it had several attendant limitations. On final drying, specimens generally exhibited shrinkage which varied within wide limits; this could have altered the internal architecture to some extent. In addition, the rupturing technique, which at the time of this investigation was the only satisfactory method of revealing the fibrillar cartilage structure, may well have had a great influence on the fibril orientations. 3. The fibrils revealed no characteristic
MRI has been suggested as an objective method of assessing anterior crucate ligament (ACL) graft “ligamentization” after reconstruction. It has been proposed that the MRI appearances could be used as an indicator of graft maturity and used as part of a return-to-sport assessment. The aim of this study was to evaluate the correlation between MRI graft signal and postoperative functional scores, anterior knee laxity, and patient age at operation. A consecutive cohort of 149 patients who had undergone semitendinosus autograft ACL reconstruction, using femoral and tibial adjustable loop fixations, were evaluated retrospectively postoperatively at two years. All underwent MRI analysis of the ACL graft, performed using signal-to-noise quotient (SNQ) and the Howell score. Functional outcome scores (Lysholm, Tegner, International Knee Documentation Committee (IKDC) subjective, and IKDC objective) were obtained and all patients underwent instrumented side-to-side anterior laxity differential laxity testing.Aims
Methods
Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses.Aims
Methods