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Bone & Joint Research
Vol. 12, Issue 7 | Pages 423 - 432
6 Jul 2023
Xie H Wang N He H Yang Z Wu J Yang T Wang Y

Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

Methods

PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 91 - 100
1 Mar 2024
Yamamoto Y Fukui T Sawauchi K Yoshikawa R Takase K Kumabe Y Maruo A Niikura T Kuroda R Oe K

Aims

Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells.

Methods

Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 375 - 386
12 Jun 2023
Li Z

Aims

Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

Methods

Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 803 - 813
1 Nov 2022
Guan X Gong X Jiao ZY Cao HY Liu S Lin C Huang X Lan H Ma L Xu B

Aims

The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.

Methods

Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 9 - 21
9 Jan 2023
Lu C Ho C Chen S Liu Z Chou PP Ho M Tien Y

Aims

The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction.

Methods

The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control media.


Bone & Joint Research
Vol. 12, Issue 11 | Pages 691 - 701
3 Nov 2023
Dai Z Chen Y He E Wang H Guo W Wu Z Huang K Zhao Q

Aims

Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Interleukin-19 (IL-19), a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. The aim of our study was to investigate the effect of IL-19 on osteoporosis.

Methods

Blood and femoral bone marrow suspension IL-19 levels were first measured in the lipopolysaccharide (LPS)-induced bone loss model. Small interfering RNA (siRNA) was applied to knock down IL-19 for further validation. Thereafter, osteoclast production was stimulated with IL-19 in combination with mouse macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The effect of IL-19 was subsequently evaluated using tartrate-resistant acid phosphatase (TRAP) staining and quantitative real-time polymerase chain reaction (RT-qPCR). The effect of IL-19 on osteoprotegerin (OPG) was then assessed using in vitro recombinant IL-19 treatment of primary osteoblasts and MLO-Y4 osteoblast cell line. Finally, transient transfection experiments and chromatin immunoprecipitation (ChIP) experiments were used to examine the exact mechanism of action.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 121 - 133
22 Feb 2022
Hsu W Lin S Hung J Chen M Lin C Hsu W Hsu WR

Aims

The decrease in the number of satellite cells (SCs), contributing to myofibre formation and reconstitution, and their proliferative capacity, leads to muscle loss, a condition known as sarcopenia. Resistance training can prevent muscle loss; however, the underlying mechanisms of resistance training effects on SCs are not well understood. We therefore conducted a comprehensive transcriptome analysis of SCs in a mouse model.

Methods

We compared the differentially expressed genes of SCs in young mice (eight weeks old), middle-aged (48-week-old) mice with resistance training intervention (MID+ T), and mice without exercise (MID) using next-generation sequencing and bioinformatics.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 820 - 829
15 Dec 2021
Schmidutz F Schopf C Yan SG Ahrend M Ihle C Sprecher C

Aims

The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD).

Methods

A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 704 - 713
1 Nov 2021
Zhang H Li J Xiang X Zhou B Zhao C Wei Q Sun Y Chen J Lai B Luo Z Li A

Aims

Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.

Methods

OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot.


Bone & Joint Research
Vol. 10, Issue 9 | Pages 611 - 618
27 Sep 2021
Ali E Birch M Hopper N Rushton N McCaskie AW Brooks RA

Aims

Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

Methods

Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization.


Bone & Joint Research
Vol. 10, Issue 9 | Pages 619 - 628
27 Sep 2021
Maestro-Paramio L García-Rey E Bensiamar F Saldaña L

Aims

To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities.

Methods

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.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 166 - 173
1 Mar 2021
Kazezian Z Yu X Ramette M Macdonald W Bull AMJ

Aims

In recent conflicts, most injuries to the limbs are due to blasts resulting in a large number of lower limb amputations. These lead to heterotopic ossification (HO), phantom limb pain (PLP), and functional deficit. The mechanism of blast loading produces a combined fracture and amputation. Therefore, to study these conditions, in vivo models that replicate this combined effect are required. The aim of this study is to develop a preclinical model of blast-induced lower limb amputation.

Methods

Cadaveric Sprague-Dawley rats’ left hindlimbs were exposed to blast waves of 7 to 13 bar burst pressures and 7.76 ms to 12.68 ms positive duration using a shock tube. Radiographs and dissection were used to identify the injuries.


Bone & Joint Research
Vol. 9, Issue 11 | Pages 827 - 839
1 Nov 2020
Hameister R Lohmann CH Dheen ST Singh G Kaur C

Aims

This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss.

Methods

TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Research
Vol. 9, Issue 11 | Pages 742 - 750
1 Nov 2020
Li L Xiang S Wang B Lin H Cao G Alexander PG Tuan RS

Aims

Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation.

Methods

We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 667 - 674
1 Oct 2020
Antich-Rosselló M Forteza-Genestra MA Calvo J Gayà A Monjo M Ramis JM

Aims

Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs).

Methods

EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca2+) content.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 406 - 413
1 Jun 2018
Shabestari M Kise NJ Landin MA Sesseng S Hellund JC Reseland JE Eriksen EF Haugen IK

Objectives. Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA. Methods. Patients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty. Results. All trapezium bones demonstrated MRI-defined BMLs. Compared with femoral heads without BMLs, the trapezia demonstrated significantly higher bone turnover (mean . sd. 0.2 (0.1) versus 0.01 (0.01) µm. 3. /µm. 2. /day), mineralizing surface (18.5% (13.1) versus 1.4% (1.3)) and vascularity (5.2% (1.1) versus 1.2% (0.6)). Femoral heads with BMLs exhibited higher bone turnover (0.3 (0.2) versus 0.2 (0.1) µm. 3. /µm. 2. /day), a higher mineralization rate (26.6% (10.6) versus 18.6% (11.9)) and greater trabecular thickness (301.3 µm (108) versus 163.6 µm (24.8)) than the trapezia. Conclusion. Bone turnover and angiogenesis were enhanced in BMLs of both the thumb base and hip OA, of which the latter exhibited the highest bone turnover. Thus, the increase in bone turnover in weight-bearing joints like the hip may be more pronounced than less mechanically loaded osteoarthritic joints demonstrating BMLs. The histological changes observed may explain the water signal from BMLs on MRI. Cite this article: M. Shabestari, N. J. Kise, M. A. Landin, S. Sesseng, J. C. Hellund, J. E. Reseland, E. F. Eriksen, I. K. Haugen. Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone Joint Res 2018;7:406–413. DOI: 10.1302/2046-3758.76.BJR-2017-0083.R3


Bone & Joint Research
Vol. 9, Issue 1 | Pages 29 - 35
1 Jan 2020
Choi J Lee YS Shim DM Seo SW

Aims

Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells.

Methods

We investigated the specific role of GNAQ using GNAQ wild-type cell lines (non-small-cell lung cancer cell lines; A549 cell lines), GNAQ knockdown cell lines, and patient-derived cancer cells. We evaluated GNAQ, RANKL, macrophage colony-stimulating factor (M-CSF), nuclear transcription factor-κB (NF-κB), inhibitor of NF-κB (IκB), and protein kinase B (Akt) signalling in the GNAQ wild-type and the GNAQ-knockdown cells. Osteoclastogenesis was also evaluated in both cell lines.


Bone & Joint Research
Vol. 8, Issue 11 | Pages 544 - 549
1 Nov 2019
Zheng W Liu C Lei M Han Y Zhou X Li C Sun S Ma X

Objectives

The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.

Methods

Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (http://analysis.bio-x.cn/) was employed.


Bone & Joint Research
Vol. 8, Issue 8 | Pages 405 - 413
1 Aug 2019
Huang J Bao X Xia W Zhu L Zhang J Ma J Jiang N Yang J Chen Q Jing T Liu J Ma D Xu G

Objectives

X-linked hypophosphataemic rickets (XLHR) is a disease of impaired bone mineralization characterized by hypophosphataemia caused by renal phosphate wasting. The main clinical manifestations of the disorder are O-shaped legs, X-shaped legs, delayed growth, and bone pain. XLHR is the most common inheritable form of rickets, with an incidence of 1/20 000 in humans. It accounts for approximately 80% of familial cases of hypophosphataemia and serves as the prototype of defective tubular phosphate (PO43+) transport, due to extra renal defects resulting in unregulated FGF23 activity. XLHR is caused by loss-of-function mutations in the PHEX gene. The aim of this research was to identify the genetic defect responsible for familial hypophosphataemic rickets in a four-generation Chinese Han pedigree and to analyze the function of this mutation.

Methods

The genome DNA samples of all members in the pedigree were extracted from whole blood. We sequenced all exons of the PHEX and FGF23 genes, as well as the adjacent splice site sequence with Sanger sequencing. Next, we analyzed the de novo mutation c.1692 del A of the PHEX gene with an online digital service and investigated the mutant PHEX with SWISS-MODEL, immunofluorescence, and protein stability detection.


Bone & Joint Research
Vol. 8, Issue 8 | Pages 397 - 404
1 Aug 2019
Osagie-Clouard L Sanghani-Kerai A Coathup M Meeson R Briggs T Blunn G

Objectives

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1).

Methods

Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34.