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Bone & Joint Research
Vol. 9, Issue 9 | Pages 613 - 622
1 Sep 2020
Perucca Orfei C Lovati AB Lugano G Viganò M Bottagisio M D’Arrigo D Sansone V Setti S de Girolamo L

Aims

In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.

Methods

A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 543 - 553
1 Sep 2020
Bakirci E Tschan K May RD Ahmad SS Kleer B Gantenbein B

Aims

The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL.

Methods

The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF).


Bone & Joint Research
Vol. 9, Issue 9 | Pages 578 - 586
1 Sep 2020
Ma M Liang X Wang X Zhang L Cheng S Guo X Zhang F Wen Y

Aims

Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD.

Methods

The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between COMP-overexpression groups and control groups were examined after cell transfection.


Objectives

Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb.

Methods

The medial and lateral cartilage samples of the tibial plateau from 12 osteoarthritis (OA) patients were collected. Ob-Rb messenger RNA (mRNA) was detected in these samples. The Ob-Rb-overexpressing chondrocytes and controls were treated with different doses of leptin for two days. The activation of the p53/p21 pathway and the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells were evaluated. The mammalian target of rapamycin (mTOR) signalling pathway and autophagy were detected after the chondrocytes were treated with a high dose of leptin.


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.


Bone & Joint Research
Vol. 9, Issue 8 | Pages 501 - 514
1 Aug 2020
Li X Yang Y Sun G Dai W Jie X Du Y Huang R Zhang J

Aims

Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method.

Methods

We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 351 - 359
1 Jul 2020
Fitzgerald J

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.


The Journal of Bone & Joint Surgery British Volume
Vol. 52-B, Issue 3 | Pages 444 - 451
1 Aug 1970
Fornasier VL

1. An unusual case of haemangiomatosis in an adult is presented. The association of angiomatosis with massive osteolysis and With extensive soft-tissue destruction is discussed. 2. The extensive vascular involvement of skin, soft tissues and bone strengthens the idea that massive osteolysis results from vascular proliferation or angiomatosis


Objectives

MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture.

Methods

Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 302 - 310
1 Jun 2020
Tibbo ME Limberg AK Salib CG Turner TW McLaury AR Jay AG Bettencourt JW Carter JM Bolon B Berry DJ Morrey ME Sanchez-Sotelo J van Wijnen AJ Abdel MP

Aims

Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.

Methods

A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein).


Bone & Joint Research
Vol. 9, Issue 1 | Pages 36 - 48
1 Jan 2020
González-Chávez SA Pacheco-Tena C Quiñonez-Flores CM Espino-Solis GP Burrola-De Anda JI Muñoz-Morales PM

Aims

To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice.

Methods

Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways.


The Journal of Bone & Joint Surgery British Volume
Vol. 48-B, Issue 4 | Pages 793 - 803
1 Nov 1966
McKibbin B Holdsworth FW

1. Experiments have been carried out in lambs to determine the source of nutrition of the joint cartilage of an immature animal. A wedge of bone with its overlying cartilage was removed from the knee joint and then replaced in its original position, so that the bone was infarcted but the cartilage remained in normal relationship with the joint. 2. In these circumstances degeneration of the cartilage occurred and proliferation ceased until revascularisation of the bone was established. 3. It is therefore concluded that growing cartilage derives a significant part of its nutrition from the underlying bone. The possibility that it also receives a contribution from synovial fluid has not been excluded


The Journal of Bone & Joint Surgery British Volume
Vol. 38-B, Issue 1 | Pages 418 - 433
1 Feb 1956
Sissons HA

1. The bone changes in four autopsied cases of Cushing's syndrome are described. The changes take the form of osteoporosis, which is most marked in the spine and the ribs. 2. The osteoporosis results from impaired osteoblastic bone formation in the presence of a normal degree of osteoclastic bone resorption. 3. Histological abnormalities of fracture callus in Cushing's syndrome indicate interference with the proliferation of osteoblasts and cartilage cells and with the formation of new tissue by these cells. 4. The bone changes in Cushing's syndrome are comparable with those produced in experimental animals by the administration of A.C.T.H. or cortisone


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


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 7 | Pages 1077 - 1081
1 Sep 2004
Tumia NS Johnstone AJ

It is well recognised that meniscal tears situated within the inner, avascular region do not heal. We investigated the potential effect of insulin-like growth factor-I (IGF-I) in promoting regeneration of meniscal tissue in the inner, middle and outer zones of the meniscus. Sheep menisci were harvested and monolayer cell cultures prepared. Various concentrations of IGF-I were used in the presence or absence of 10% fetal calf serum (FCS). We measured the uptake of radioactive thymidine, sulphur, and proline to assess cell proliferation and formation of extracellular matrix (ECM). IGF-I, in the presence or absence of FCS, increased the formation of DNA and ECM in all meniscal zones. However, the response of the cells from the avascular zone was greater than that from the vascular zone. Our findings indicate that fibrochondrocytes cultured from avascular meniscal tissue have the ability to regenerate when exposed to anabolic cytokines such as IGF-I


The Journal of Bone & Joint Surgery British Volume
Vol. 48-B, Issue 3 | Pages 441 - 447
1 Aug 1966
Sanerkin NG Edwards P

1. A case is described of severe birth injury to the sternomastoid muscle in a breech-delivered two-day-old infant. The affected muscle showed widespread haemorrhage, fragmentation and necrosis of its fibres, and disruption and disorganisation of the endomysial sheaths. 2. Disruptive muscular trauma of this type is known to lead to florid fibroblastic proliferation with formation of a large mass of scar tissue. It is suggested that the "sternomastoid tumour" of infancy develops as a sequel to such trauma occurring during birth. 3. The theories of birth trauma and of ischaemia, in the etiology of the "sternomastoid tumour" of infancy and of congenital muscular torticollis, are not mutually exclusive but may be complementary, the circumstances causing the trauma also leading to ischaemic damage


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 3 | Pages 457 - 460
1 Apr 2000
Zambonin G Camerino C Greco G Patella V Moretti B Grano M

We have studied in vitro the effect of a hydroxyapatite (HA) tricalcium phosphate material coated with hepatocyte growth factor (HA-HGF) on cell growth, collagen synthesis and secretion of metalloproteinases (MMPs) by human osteoblasts. Cell proliferation was stimulated when osteoblasts were incubated with untreated HA and was further increased after exposure to HA-HGF. The uptake of [. 3. H]-proline was increased after treatment with HA. When osteoblasts were exposed to HA-HGF, collagen synthesis was increased with respect to HA. The secretion of MMPs in control cells was undetectable, but in HA and HA-HGF cells MMP 2 and MMP 9 were clearly synthesised. Our results suggest that HA can promote osteoblast activity and that HGF can further increase its bioactivity


The Journal of Bone & Joint Surgery British Volume
Vol. 68-B, Issue 3 | Pages 483 - 488
1 May 1986
Sakurai M Miyasaka Y

Thickening of the fibrous element of a peripheral nerve may be caused by repeated friction, traction, constriction, ischaemia or partial rupture. The sequel may be a conduction disorder and a clinical condition such as an entrapment neuropathy or a tardy nerve palsy. Neural fibrosis is typically associated with a pseudoneuroma in continuity which has resulted from scarring and adhesions around the nerve as well as proliferation of the fibrous element within the nerve; the fibrosis may be classified as extraneural, intraneural or dispersive. We report 17 cases treated by external neurolysis, with 14 satisfactory results, and 42 patients treated by internal neurolysis with success in 37. Seven of the eight failures were in cases of dispersive fibrosis. A technique of internal neurolysis is described


The Journal of Bone & Joint Surgery British Volume
Vol. 55-B, Issue 3 | Pages 545 - 565
1 Aug 1973
Schajowicz F Slullitel J

1. The clinical, radiological and pathological features of 106 cases of eosinophilic granuloma of bone (solitary and multiple) are reported. 2. Our findings support strongly the concept that eosinophilic granuloma, Hand-Schüller-Christian and Letterer-Siwe syndrome are closely related manifestations of a single pathological disorder, characterised fundamentally by the proliferation of non-neoplastic histiocytes, intermingled with a variable amount of eosinophilic leucocytes and other inflammatory elements. 3. Lipid-bearing histiocytes (xanthoma cells) may be found in variable amounts in solitary and multiple lesions but are more abundant in the more extensive or chronic lesions of Hand-Schüller-Christian syndrome. 4. These entities may perhaps represent some type of immuno-allergic (hypersensitive) reaction to a still unknown infection, possibly viral


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 3 | Pages 409 - 416
1 Mar 2009
Anders JO Mollenhauer J Beberhold A Kinne RW Venbrocks RA

The gelatin-based haemostyptic compound Spongostan was tested as a three-dimensional (3D) chondrocyte matrix in an in vitro model for autologous chondrocyte transplantation using cells harvested from bovine knees. In a control experiment of monolayer cultures, the proliferation or de-differentiation of bovine chondrocytes was either not or only marginally influenced by the presence of Spongostan (0.3 mg/ml). In monolayers and 3-D Minusheet culture chambers, the cartilage-specific differentiation markers aggrecan and type-II collagen were ubiquitously present in a cell-associated fashion and in the pericellular matrix. The Minusheet cultures usually showed a markedly higher mRNA expression than monolayer cultures irrespective of whether Spongostan had been present or not during culture. Although the de-differentiation marker type-I collagen was also present, the ratio of type-I to type-II collagen or aggrecan to type-I collagen remained higher in Minusheet 3-D cultures than in monolayer cultures irrespective of whether Spongostan had been included in or excluded from the monolayer cultures. The concentration of GAG in Minusheet cultures reached its maximum after 14 days with a mean of 0.83 ± 0.8 μg/10. 6. cells; mean ±, . sem. , but remained considerably lower than in monolayer cultures with/without Spongostan. Our results suggest that Spongostan is in principle suitable as a 3-D chondrocyte matrix, as demonstrated in Minusheet chambers, in particular for a culture period of 14 days. Clinically, differentiating effects on chondrocytes, simple handling and optimal formability may render Spongostan an attractive 3-D scaffold for autologous chondrocyte transplantation