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The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 1 | Pages 139 - 143
1 Jan 2001
Fini M Giavaresi G Torricelli P Krajewski A Ravaglioli A Belmonte MM Biagini G Giardino R

We implanted nails made of titanium (Ti6Al4V) and of two types of glass ceramic material (RKKP and AP40) into healthy and osteopenic rats. After two months, a histomorphometric analysis was performed and the affinity index calculated. In addition, osteoblasts from normal and osteopenic bone were cultured and the biomaterials were evaluated in vitro. In normal bone the rate of osseointegration was similar for all materials tested (p > 0.5) while in osteopenic bone AP40 did not osseointegrate (p > 0.0005). In vitro, no differences were observed for all biomaterials when cultured in normal bone-derived cells whereas in osteopenic-bone-derived cells there was a significant difference in some of the tested parameters when using AP40. Our findings suggest that osteopenic models may be used in vivo in the preclinical evaluation of orthopaedic biomaterials. We suggest that primary cell cultures from pathological models could be used as an experimental model in vitro


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 3 | Pages 452 - 456
1 Apr 2002
Yang TT Sabokbar A Gibbons CLMH Athanasou NA

The cellular mechanisms which account for the formation of osteoclasts and bone resorption associated with enlarging benign and malignant mesenchymal tumours of bone are uncertain. Osteoclasts are marrow-derived, multinucleated, bone-resorbing cells which express a macrophage phenotype. We have determined whether tumour-associated macrophages (TAMs) isolated from benign and malignant mesenchymal tumours are capable of differentiating into osteoclasts. Macrophages were cultured on both coverslips and dentine slices for up to 21 days with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D. 3. (1,25(OH). 2. D. 3. ) and human macrophage colony-stimulating factor (M-CSF) or, in the absence of UMR 106 cells, with M-CSF and RANK ligand. In all tumours, the formation of osteoclasts from CD14-positive macrophages was shown by the formation of tartrate-resistant-acid-phosphatase and vitronectin-receptor-positive multinucleated cells which were capable of carrying out lacunar resorption. These results indicate that the tumour osteolysis associated with the growth of mesenchymal tumours in bone is likely to be due in part to the differentiation of mononuclear phagocyte osteoclast precursors which are present in the TAM population of these lesions


Bone & Joint Research
Vol. 9, Issue 12 | Pages 857 - 869
1 Dec 2020
Slullitel PA Coutu D Buttaro MA Beaule PE Grammatopoulos G

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells.

Cite this article: Bone Joint Res 2020;9(12):857–869.


The Journal of Bone & Joint Surgery British Volume
Vol. 43-B, Issue 1 | Pages 152 - 161
1 Feb 1961
Hancox NM Owen R Singleton A

1. Cancellous bone cubes from calf and man were deproteinised with hydrogen peroxide and with ethylenediamine. 2. Long bones were removed aseptically from sheep, stored in the bone bank and used for cancellous homografts. 3. Holes were drilled in the upper part of the tibia or ulna or in the lower part of the femur of sheep. Some were left empty; others were filled with plugs of the deproteinised heterogenous bone, with autografts, or with homografts. 4. Histological appearances were studied after seventeen and thirty-six days. 5. At seventeen days repair was more advanced in the plugged holes; the biological result was better with the ethylenediamine-treated than with the peroxide-treated material. After thirty-six days repair was at an advanced stage. As much new bone had been deposited on the trabeculae of the deproteinised heterografts as on those of the homografts. 6. There was no evidence of metaplastic bone formation; new bone seemed to form from endosteal osteoblasts. 7. Certain clinical implications are briefly discussed


The Journal of Bone & Joint Surgery British Volume
Vol. 51-B, Issue 1 | Pages 165 - 174
1 Feb 1969
Rösingh GE James J

1. An investigation was made of the tolerance of the cells in the femoral head in rabbits for ischaemia brought about by transecting the ligament of the femoral head and applying a ligature around the femoral neck. The animals were killed two, six, twelve, twenty-four and seventy-two hours after operation. 2. In the cells of the bone marrow and in the osteoblasts distinct histological signs of disintegration were present six hours after operation. Pyknosis of the osteocyte nuclei was found after twenty-four hours' ischaemia; sometimes vacuolar clarifications could be observed in these pyknotic nuclei. After three days of ischaemia the staining affinity for Feulgen and haematoxylin of a number of osteocyte nuclei had visibly decreased. 3. The Feulgen-DNA content of the osteocyte nuclei-as measured in individual nuclei by means of an integrated microdensitometer-was significantly reduced as compared with similar nuclei from the control side as early as after six hours of ischaemia. This DNA loss was progressive with the period of ischaemia. From these facts, the conclusion was reached that in the femoral head of the rabbit the period of reversible damage for osteocytes must have ended within six hours


The Bone & Joint Journal
Vol. 102-B, Issue 4 | Pages 403 - 406
1 Apr 2020
Trompeter A


Bone & Joint Research
Vol. 9, Issue 11 | Pages 798 - 807
2 Nov 2020
Brzeszczyńska J Brzeszczyński F Hamilton DF McGregor R Simpson AHRW

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data.

Cite this article: Bone Joint Res 2020;9(11):798–807.


The Journal of Bone & Joint Surgery British Volume
Vol. 39-B, Issue 1 | Pages 134 - 144
1 Feb 1957
Scott JH

1. Bones consist essentially of bundles of collagenous fibres united by a cementing substance in which the inorganic material lies in the form of minute plate-like crystals. 2. During weight bearing and muscle action bones as a whole are deformed to a variable extent. Periods of deformation are followed by periods of relaxed pressure during which the bones tend to return to their normal form. 3. These variations in deformation and elastic recoil set up alternating pressures and tensions within the bones along the bone cyrstal encrusted fibres which make up the trabeculae, lamellae and Haversian systems, and these alternating phases of compression and tension stimulate the activity of osteoblasts so that bone formation predominates over bone resorption. 4. These alterations of pressure and tension are intermittent and reciprocal in nature and do not, as postulated by the trajectorial theory, involve different trabeculae, nor is it necessary to consider whether tension or pressure is the more important phase in determining bone deposition. 5. The pressure exerted by cysts, tumours, erupting teeth, etc., is of a quite different nature, as is the response to trauma or callus formation in the healing of fractures. These processes are essentially vascular phenomena involving localised areas of bony tissue and not bones as mechanical units


Bone & Joint Open
Vol. 1, Issue 9 | Pages 576 - 584
18 Sep 2020
Sun Z Liu W Li J Fan C

Post-traumatic elbow stiffness is a disabling condition that remains challenging for upper limb surgeons. Open elbow arthrolysis is commonly used for the treatment of stiff elbow when conservative therapy has failed. Multiple questions commonly arise from surgeons who deal with this disease. These include whether the patient has post-traumatic stiff elbow, how to evaluate the problem, when surgery is appropriate, how to perform an excellent arthrolysis, what the optimal postoperative rehabilitation is, and how to prevent or reduce the incidence of complications. Following these questions, this review provides an update and overview of post-traumatic elbow stiffness with respect to the diagnosis, preoperative evaluation, arthrolysis strategies, postoperative rehabilitation, and prevention of complications, aiming to provide a complete diagnosis and treatment path.

Cite this article: Bone Joint Open 2020;1-9:576–584.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 6 | Pages 912 - 915
1 Aug 2001
Salai M Segal E Cohen I Dudkiewicz I Farzame N Pitaru S Savion N

Colchicine is often used in the treatment of diseases such as familial Mediterranean fever (FMF) and gout. We have previously reported that patients with FMF who had colchicine on a daily basis and who had a total hip arthroplasty showed no heterotopic ossification after surgery. The mechanism by which colchicine causes this clinical phenomenon has never been elucidated. We therefore evaluated the effect of various concentrations of colchicine on cell proliferation and mineralisation in tissue culture, using rat and human cells with and without osteogenic potential. Cell proliferation was assessed by direct cell counts and uptake of (. 3. H)thymidine, and mineralisation by measuring the amount of staining by Alizarin Red. Our findings indicate that concentrations of colchicine of up to 3 ng/ml did not affect cell proliferation but inhibition was observed at 10 to 30 ng/ml. Mineralisation decreased to almost 50%, which was the maximum inhibition observed, at concentrations of colchicine of 2.5 ng/ml. These results indicate that colchicine at low concentrations, of up to 3 ng/ml, has the capacity to inhibit selectively bone-like cell mineralisation in culture, without affecting cell proliferation. Further clinical and laboratory studies are necessary to evaluate the effects of colchicine on biological processes involving the proliferation of osteoblasts and tissue mineralisation in vivo, such as the healing of fractures, the formation of heterotopic bone and neoplastic bone growth


The Journal of Bone & Joint Surgery British Volume
Vol. 36-B, Issue 3 | Pages 474 - 489
1 Aug 1954
Schajowicz F Cabrini RL

1. Histochemical studies have been made of the distribution of alkaline phosphatase, glycogen and acid mucopolysaccharides in normal growing bones (mice, rats and men) and also in forty cases of pathological bone processes (neoplastic and dystrophic). 2. The study of normal material confirmed that alkaline phosphatase is plentiful in calcification of cartilage and even more plentiful in bone formation (whether enchondral or direct). 3. It was observed that glycogen increased in the cartilage areas about to be calcified, and that it disappeared in those calcified. It seemed that osteoblasts did not always contain glycogen. 4. In the pathological material (tumours and dystrophic processes) there was great phosphatase activity in the osteogenic areas and also in the cartilage about to be calcified. Whereas glycogen was plentiful in some cases of neoplastic or reactive osteogenesis, it was absent from others. 5. In every area of normal or pathological ossification, the presence of phosphatase seems to be a rule; glycogen is often but not always present. 6. It appears that alkaline phosphatase plays an important role in the formation of the protein matrix of bone, but is not associated with the elaboration of the mucoprotein cartilage matrix. We believe it is premature to draw any definite conclusion on the behaviour and role of the metachromatic substances in the processes of calcification and ossification. The histochemical study of alkaline phosphatase has shown that this is a valuable method in the detection of reactionary or pathological osteogenic processes which in some cases are difficult to demonstrate with the usual histological methods


The Journal of Bone & Joint Surgery British Volume
Vol. 49-B, Issue 1 | Pages 146 - 153
1 Feb 1967
Lee WR

1 . Normal and diseased bone was obtained by biopsy from five patients suffering from Paget's disease. The tissue was studied by histology, microradiography and quantitative fluorescence microscopy using tetracycline markers. Study of the morphological changes showed that two of the biopsies could be regarded as normal, while one was osteoporotic; two biopsy specimens were in the porotic phase of Paget's disease and the remaining five were in the sclerotic phase. 2. The tetracycline markers were used to measure the linear rate at which bone was deposited on individual surfaces (appositional growth rate) in µ per day and the percentage volume of new bone added to the total volume of bone per day (bone formation rate). The values obtained for appositional growth rate in all the biopsies were of the order of 1 µ per day, but slightly higher values were obtained in the diseased tissue of each individual. The bone formation rate in normal bone from the proximal femur was about 0·04 per cent per day, about 0·13 per cent per day in the porotic phase, and about 0·4 per cent per day in the sclerotic phase of Paget's disease. 3. Although these values must be accepted with some reservation, there seems to be no doubt that there is an upper limit of about 1 µ per day to the rate of deposition of bone on an individual bone surface; this suggests that in Paget's disease the osteoblast behaves as a normal cell


Bone & Joint Research
Vol. 9, Issue 3 | Pages 99 - 107
1 Mar 2020
Chang C Jou I Wu T Su F Tai T

Aims

Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.

Methods

We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests.


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 3 | Pages 531 - 537
1 May 1999
Corbett SA Hukkanen M Batten J McCarthy ID Polak JM Hughes SPF

Our aim was to investigate whether nitric oxide synthase (NOS) isoforms, responsible for the generation of NO, are expressed during the healing of fractures. To localise the sites of expression compared with those in normal bone we made standardised, stabilised, unilateral tibial fractures in male Wistar rats. Immunostaining was used to determine the precise tissue localisation of the different NOS isoforms. Western blotting was used to assess expression of NOS isoform protein and L-citrulline assays for studies on NOS activity. Control tissue was obtained from both the contralateral uninjured limb and limbs of normal rats. Immunohistochemistry showed increased expression of endothelial NOS (eNOS) to be strongest in the cortical blood vessels and in osteocytes in the early phase of fracture repair. Western blot and image analysis confirmed this initial increase. Significantly elevated calcium-dependent NOS activity was observed at day 1 after fracture. Inducible NOS (iNOS) was localised principally in endosteal osteoblasts and was also seen in chondroblasts especially in the second week of fracture healing. Western blotting showed a reduction in iNOS during the early healing period. Significantly reduced calcium-independent NOS activity was also seen. No neuronal NOS was seen in either fracture or normal tissue. Increased eNOS in bone blood vessels is likely to mediate the increased blood flow recognised during fracture healing. eNOS expression in osteocytes may occur in response to changes in either mechanical or local fluid shear stress. The finding that eNOS is increased and iNOS reduced in early healing of fractures may be important in their successful repair


Bone & Joint Research
Vol. 9, Issue 2 | Pages 71 - 76
1 Feb 2020
Gao T Lin J Zhang C Zhu H Zheng X

Aims

The purpose of this study was to determine whether intracellular Staphylococcus aureus is associated with recurrent infection in a rat model of open fracture.

Methods

After stabilizing with Kirschner wire, we created a midshaft femur fracture in Sprague-Dawley rats and infected the wound with green fluorescent protein (GFP)-tagged S. aureus. After repeated debridement and negative swab culture was achieved, the isolation of GFP-containing cells from skin, bone marrow, and muscle was then performed. The composition and viability of intracellular S. aureus in isolated GFP-positive cells was assessed. We suppressed the host immune system and observed whether recurrent infection would occur. Finally, rats were assigned to one of six treatment groups (a combination of antibiotic treatment and implant removal/retention). The proportion of successful eradication was determined.


The Journal of Bone & Joint Surgery British Volume
Vol. 65-B, Issue 3 | Pages 299 - 307
1 May 1983
Schajowicz F Santini Araujo E Berenstein M

Out of 21 900 cases filed at the Latin-American Registry of Bone Pathology between April 1940 and July 1981, there were 987 with Paget's disease (4.51 per cent); 62 of these (6.28 per cent) were complicated by sarcoma and two were associated with giant-cell tumours of bone (osteoclastoma) without signs of malignancy. There was a slight predominance of men and the ages ranged from 45 to 87 years, with an average of 66 years. The most frequent sites were the femur (23 cases), the humerus (nine), the pelvis (10), and the tibia (nine). The low incidence of vertebral involvement (five cases) is noteworthy and is in sharp contrast to uncomplicated Paget's disease. The most common tumour type was osteosarcoma (39 cases), followed by fibrosarcoma (15 cases); other varieties (chondrosarcoma, malignant fibrous histiocytoma and reticulum-cell sarcoma) were much rarer. Most of the sarcomata occurred when the Paget's disease was polyostotic. Tumours often developed simultaneously, or at short time intervals, in the same or different bones; these bones had, in all cases, been affected by Paget's disease. The histological features of the osteosarcomata were characteristic, with large numbers of osteoclast giant cells, alternating with atypical osteoblasts, thus exaggerating the anarchic remodelling process of Paget's disease. The neighbouring areas of the pagetic bone showed an increased number of osteoclasts. These facts suggest a possible pathogenetic relationship between sarcoma and Paget's disease; the possibility of both processes having a viral aetiology is discussed


The Journal of Bone & Joint Surgery British Volume
Vol. 37-B, Issue 2 | Pages 266 - 303
1 May 1955
Thomson AD Turner-Warwick RT

1. One hundred and seventy-nine cases of primary malignant bone tumour and giant-cell tumour seen at the Middlesex Hospital since 1925 are reviewed. Tumours arising from non-skeletal tissues in bone have been excluded. 2. The following histological classification is used. Osteosarcoma (osteoblast sarcoma): This tumour is not synonymous with osteogenic (bone-forming) sarcoma. The essential feature is the formation of osteoid tissue by malignant osteoblasts, with no intermediate matrix of cartilage or fibrous tissue. It is the most malignant bone tumour and only four of the thirty-two patients survived three years. Chondrosarcoma: These tumours are composed of cartilage, and some show secondary ossification. The behaviour of this group is related to the degree of cartilaginous differentiation. In general, compared with the osteosarcoma, it is of low-grade malignancy. More than half of the sixty-eight patients survived four years. Fibrosarcoma: The essential feature of this tumour is the production of collagen by malignant fibroblastic tumour cells. Tumours of this type invading the medullary cavity have an average prognosis between that of an osteosarcoma and a chondrosarcoma. Nine of the thirty-four patients survived three years. Spindle-cell sarcoma: These tumours are composed of spindle cells which produce no diagnostic matrix. In spite of the lack of differentiation the outlook is not hopeless. Six of the eleven patients survived for five years or more. Giant-cell tumour: This tumour is composed of a cellular stroma with diagnostic giant cells resembling osteoclasts. It is by no means a benign lesion, for half the tumours recurred after treatment and a quarter of the patients died with metastases. 3. The subdivision of primary malignant skeletal tumours into groups according to the histological pattern appears to be reflected in the behaviour of the individual tumours after treatment. The prognosis of each group has been stated in the appropriate sections


Bone & Joint Research
Vol. 9, Issue 9 | Pages 601 - 612
1 Sep 2020
Rajagopal K Ramesh S Walter NM Arora A Katti DS Madhuri V

Aims

Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.

Methods

Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.


The Bone & Joint Journal
Vol. 102-B, Issue 7 Supple B | Pages 122 - 128
1 Jul 2020
Sodhi N Acuna A Etcheson J Mohamed N Davila I Ehiorobo JO Jones LC Delanois RE Mont MA

Aims

Earlier studies dealing with trends in the management of osteonecrosis of the femoral head (ONFH) identified an increasing rate of total hip arthroplasties (THAs) and a decreasing rate of joint-preserving procedures between 1992 and 2008. In an effort to assess new trends in the management of this condition, this study evaluated the annual trends of joint-preserving versus arthroplasties for patients aged < or > 50 years old, and the incidence of specific operative management techniques.

Methods

A total of 219,371 patients with ONFH were identified from a nationwide database between 1 January 2009 and 31 December 2015. The mean age was 54 years (18 to 90) and 105,298 (48%) were female. The diagnosis was made using International Classification of Disease, Ninth revision, Clinical Modification (ICD-9-CM) and Tenth Revision, Clinical Modification (ICD-10-CM) procedure codes. The percentage of patients managed using each procedure during each year was calculated and compared between years. The trends in the use of the types of procedure were also evaluated.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 73 - 80
1 Feb 2019
Zhang J Hao X Yin M Xu T Guo F

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.