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Bone & Joint Research
Vol. 14, Issue 2 | Pages 97 - 110
6 Feb 2025
Zhang D Zhu T Bai J Chen C Wen J Zhou Y Guan X

Aims

In our previous research, we have found that melatonin (MEL) affects the osteoporotic process. By balancing bone remoulding, autophagy is involved in age-related bone loss. However, as a regulator of autophagy, whether MEL influences senile osteoporosis via regulating autophagy remains unclear.

Methods

Cellular, radiological, and histopathological evaluations were performed on 36 16-month-old male C57BL6/L mice or aged bone marrow-derived mesenchymal stem cells. A MEL-gelatin methacrylamide system was constructed to aid osteoporotic fracture healing.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 77 - 92
4 Feb 2025
Spanninga BJ Hoelen TA Johnson S Cheng B Blokhuis TJ Willems PC Arts JJC

Aims

Autologous bone graft (ABG) is considered the ‘gold standard’ among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system.

Methods

PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant articles on 13 May 2023. The systematic review was reported according to the PRISMA guidelines. Two reviewers independently screened and assessed the identified articles. Quality assessment was conducted using the methodological index for non-randomized studies and the risk of bias assessment tool for randomized controlled trials.


Bone & Joint Research
Vol. 14, Issue 1 | Pages 33 - 41
17 Jan 2025
Fujimoto K Kanamoto T Otani S Miyazaki R Ebina K Nakata K

Aims. Ultrasound-guided injection techniques are expected to enhance therapeutic efficacy for skeletal muscle injuries and disorders, but basic knowledge is lacking. The purpose of this study was to examine the diagnostic accuracy of ultrasound for abnormal skeletal muscle lesions, and to examine the distribution patterns of solution and cells injected into abnormal muscle lesions under ultrasound guidance. Methods. A cardiotoxin (CTX)-induced muscle injury model was used. Briefly, CTX was injected into tibialis anterior muscle in rats under ultrasound observation. First, the diagnostic accuracy of abnormal muscle lesions on ultrasound was examined by comparing ultrasound findings and histology. Next, Fast Green solution and green fluorescent protein (GFP)-labelled cells were simultaneously injected into the abnormal muscle lesions under ultrasound guidance, and their distribution was evaluated. Results. Evaluation of short-axis ultrasound images and cross-sectional histological staining showed a strong correlation (r = 0.927; p < 0.001) between the maximum muscle damage area in ultrasound and haematoxylin and eosin (H&E) staining evaluations. Histological analysis showed that ultrasound-guided injection could successfully deliver Fast Green solution around the myofibres at the site of injury. In contrast, the distribution of injected cells was very localized compared to the area stained with Fast Green. Conclusion. This experimental animal study demonstrated the potential of ultrasound to quantitatively visualize abnormalities of skeletal muscle. It also showed that ultrasound-guided injections allowed for highly accurate distribution of solution and cells in abnormal muscle tissue, but the patterns of solution and cell distribution were markedly different. Although future studies using a more clinically relevant model are necessary, these results are important findings when considering biological therapies for skeletal muscle injuries and disorders. Cite this article: Bone Joint Res 2025;14(1):33–41


Bone & Joint Research
Vol. 14, Issue 1 | Pages 20 - 32
17 Jan 2025
Chen Z Zhou T Yin Z Duan P Zhang Y Feng Y Shi R Xu Y Pang R Tan H

Aims

Magnesium ions (Mg2+) play an important role in promoting cartilage repair in cartilage lesions. However, no research has focused on the role of Mg2+ combined with microfracture (MFX) in hyaline-like cartilage repair mediated by cartilage injury. This study aimed to investigate the beneficial effects of the combination of MFX and Mg2+ in cartilage repair.

Methods

A total of 60 rabbits were classified into five groups (n = 12 each): sham, MFX, and three different doses of Mg2+ treatment groups (0.05, 0.5, and 5 mol/L). Bone cartilage defects were created in the trochlear groove cartilage of rabbits. MFX surgery was performed after osteochondral defects. Mg2+ was injected into knee joints immediately and two and four weeks after surgery. At six and 12 weeks after surgery, the rabbits were killed. Cartilage damage was detected by gross observation, micro-CT, and histological analysis. The expression levels of related genes were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).


Bone & Joint Research
Vol. 14, Issue 1 | Pages 5 - 15
1 Jan 2025
Tanveer M Klein K von Rechenberg B Darwiche S Dailey HL

Aims

The “2 to 10% strain rule” for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization.

Methods

MicroCT scans of eight female sheep with plated mid-shaft tibial osteotomies were used to create image-based finite element models. Virtual mechanical testing was used to compute postoperative gap-closing and 3D continuum strains representing compression (volumetric strain) and shear deformation (distortional strain). Callus mineralization was measured in zones in and around the osteotomy gap.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 790 - 792
17 Dec 2024
Mangwani J Brockett C Pegg E

Cite this article: Bone Joint Res 2024;13(12):790–792.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 779 - 789
16 Dec 2024
Zou H Hu F Wu X Xu B Shang G An D Qin D Zhang X Yang A

Aims

The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

Methods

Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 764 - 778
12 Dec 2024
Huang Q Zhuo Y Duan Z Long Y Wang J Zhang Z Fan S Huang Y Deng K Xin H

Aims

Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.

Methods

In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 750 - 763
11 Dec 2024
Xie C Gong J Zheng C Zhang J Gao J Tian C Guo X Dai S Gao T

Aims

This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

Methods

The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 725 - 740
5 Dec 2024
Xing J Liu S

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 703 - 715
3 Dec 2024
Raza IGA Snelling SJB Mimpen JY

Aims. Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease. Methods. A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed. Results. A total of 161 studies were included, which covered capsule, ligaments, meniscus, skeletal muscle, synovium, and tendon in both humans and animals, and fat pad and intervertebral disc in humans only. These studies covered a wide variety of ECM features, including individual ECM components (i.e. collagens, proteoglycans, and glycoproteins), ECM architecture (i.e. collagen fibre organization and diameter), and viscoelastic properties (i.e. elastic and compressive modulus). Some ECM changes, notably calcification and the loss of collagen fibre organization, have been extensively studied across osteoarthritic tissues. However, most ECM features were only studied by one or a few papers in each tissue. When comparisons were possible, the results from animal experiments largely concurred with those from human studies, although some findings were contradictory. Conclusion. Changes in ECM composition and architecture occur throughout non-cartilage soft tissues in the osteoarthritic joint, but most of these remain poorly defined due to the low number of studies and lack of healthy comparator groups. Cite this article: Bone Joint Res 2024;13(12):703–715


Bone & Joint Research
Vol. 13, Issue 12 | Pages 695 - 702
1 Dec 2024
Cordero García-Galán E Medel-Plaza M Pozo-Kreilinger JJ Sarnago H Lucía Ó Rico-Nieto A Esteban J Gomez-Barrena E

Aims

Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting.

Methods

Titanium-aluminium-vanadium (Ti6Al4V) screws were implanted in medial condyle of New Zealand giant rabbit knee. Study intervention consisted of induction heating of the screw head up to 70°C for 3.5 minutes after implantation using a portable device. Both knees were implanted, and induction heating was applied unilaterally keeping contralateral knee as paired control. Sterile screws were implanted in six rabbits, while the other six received screws coated with Staphylococcus aureus biofilm. Sacrifice and sample collection were performed 24, 48, or 96 hours postoperatively. Retrieved screws were sonicated, and adhered bacteria were estimated via drop-plate. Width of bone necrosis in retrieved femora was assessed through microscopic examination. Analysis was performed using non-parametric tests with significance fixed at p ≤ 0.05.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 659 - 672
20 Nov 2024
Mo H Sun K Hou Y Ruan Z He Z Liu H Li L Wang Z Guo F

Aims

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Methods

A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 632 - 646
7 Nov 2024
Diaz Dilernia F Watson D Heinrichs DE Vasarhelyi E

Aims

The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against Staphylococcus aureus.

Methods

We performed in vitro growth and viability assays to determine the capability of S. aureus to survive in SF with the addition of 10 µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated its sensitivity to killing, comparing wild type (WT) and CopAZB-deficient USA300 strains.


Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Methods

Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 103 or 1 × 106 colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 103 or 1 × 106 CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims

This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.

Methods

Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).


Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Methods

Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 559 - 572
8 Oct 2024
Wu W Zhao Z Wang Y Liu M Zhu G Li L

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Methods

A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 546 - 558
4 Oct 2024
Li Y Wuermanbieke S Wang F Mu W Ji B Guo X Zou C Chen Y Zhang X Cao L

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Methods

A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 535 - 545
2 Oct 2024
Zou C Guo W Mu W Wahafu T Li Y Hua L Xu B Cao L

Aims

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

Methods

We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography.