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The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 12 | Pages 1635 - 1640
1 Dec 2008
Spence G Phillips S Campion C Brooks R Rushton N

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model. Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively. After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 978 - 985
1 Sep 2024
Savoie III FH Delvadia BP Tate JP Winter JE Williams GH Sherman WF O’Brien MJ

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 121 - 132
1 Feb 2023
Mo H Wang Z He Z Wan J Lu R Wang C Chen A Cheng P

Aims

Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA.

Methods

After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 433 - 446
7 Jul 2023
Guo L Guo H Zhang Y Chen Z Sun J Wu G Wang Y Zhang Y Wei X Li P

Aims

To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis.

Methods

Empty adenovirus (EP) and a HDAC4 overexpression adenovirus were transfected into cultured human chondrocytes. The cell survival rate was examined by real-time cell analysis (RTCA) and EdU and flow cytometry assays. Cell biofunction was detected by Western blotting. The expression profiles of messenger RNAs (mRNAs) in the EP and HDAC4 transfection groups were assessed using whole-transcriptome sequencing (RNA-seq). Volcano plot, Gene Ontology, and pathway analyses were performed to identify differentially expressed genes (DEGs). For verification of the results, the A289E/S246/467/632 A sites of HDAC4 were mutated to enhance the function of HDAC4 by increasing HDAC4 expression in the nucleus. RNA-seq was performed to identify the molecular mechanism of HDAC4 in chondrocytes. Finally, the top ten DEGs associated with ribosomes were verified by quantitative polymerase chain reaction (QPCR) in chondrocytes, and the top gene was verified both in vitro and in vivo.


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.


Aims

Osteochondral lesions of the talus (OLT) are a common cause of disability and chronic ankle pain. Many operative treatment strategies have been introduced; however, they have their own disadvantages. Recently lesion repair using autologous cartilage chip has emerged therefore we investigated the efficacy of particulated autologous cartilage transplantation (PACT) in OLT.

Methods

We retrospectively analyzed 32 consecutive symptomatic patients with OLT who underwent PACT with minimum one-year follow-up. Standard preoperative radiography and MRI were performed for all patients. Follow-up second-look arthroscopy or MRI was performed with patient consent approximately one-year postoperatively. Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) score and International Cartilage Repair Society (ICRS) grades were used to evaluate the quality of the regenerated cartilage. Clinical outcomes were assessed using the pain visual analogue scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Scale (FAOS).


Bone & Joint Research
Vol. 12, Issue 8 | Pages 504 - 511
23 Aug 2023
Wang C Liu S Chang C

Aims

This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model.

Methods

A total of 36 porcine calcanea were sawed to create simple avulsion fractures with three different fragment thicknesses (5, 10, and 15 mm). They were randomly fixed with either two suture anchors or one headless screw. Load-to-failure and cyclic loading tension tests were performed for the biomechanical analysis.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 110 - 123
7 Mar 2024
Xu J Ruan Z Guo Z Hou L Wang G Zheng Z Zhang X Liu H Sun K Guo F

Aims

Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear.

Methods

In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression.


Bone & Joint Research
Vol. 4, Issue 5 | Pages 70 - 77
1 May 2015
Gupta A Liberati TA Verhulst SJ Main BJ Roberts MH Potty AGR Pylawka TK El-Amin III SF

Objectives. The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. Methods. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. Results. No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Conclusions. Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70–7


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 360
Vol. 14, Issue 1 | Pages 46 - 47
1 Feb 2025

The February 2025 Research Roundup360 looks at: Walk your way to longer life: quantifying physical activity’s role in extending longevity; Is information about musculoskeletal malignancies from large language models or web resources at a suitable reading level for patients?; Contemporary surgical management of osteosarcoma and Ewing’s sarcoma; L-arginine and tendon healing; What you can’t hear might not stress you out as much.


Objectives. Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods. ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results. Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion. The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2


Bone & Joint Research
Vol. 2, Issue 8 | Pages 169 - 178
1 Aug 2013
Rodrigues-Pinto R Richardson SM Hoyland JA

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc. Cite this article: Bone Joint Res 2013;2:169–78


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 801 - 807
1 Jul 2023
Dietrich G Terrier A Favre M Elmers J Stockton L Soppelsa D Cherix S Vauclair F

Aims

Tobacco, in addition to being one of the greatest public health threats facing our world, is believed to have deleterious effects on bone metabolism and especially on bone healing. It has been described in the literature that patients who smoke are approximately twice as likely to develop a nonunion following a non-specific bone fracture. For clavicle fractures, this risk is unclear, as is the impact that such a complication might have on the initial management of these fractures.

Methods

A systematic review and meta-analysis were performed for conservatively treated displaced midshaft clavicle fractures. Embase, PubMed, and Cochrane Central Register of Controlled Trials (via Cochrane Library) were searched from inception to 12 May 2022, with supplementary searches in Open Grey, ClinicalTrials.gov, ProQuest Dissertations & Theses, and Google Scholar. The searches were performed without limits for publication date or languages.


Bone & Joint Open
Vol. 5, Issue 12 | Pages 1101 - 1107
11 Dec 2024
Haas-Lützenberger EM Emelianova I Bader MC Mert S Moellhoff N Demmer W Berger U Giunta R

Aims

In the treatment of basal thumb osteoarthritis (OA), intra-articular autologous fat transplantation has become of great interest within recent years as a minimally invasive and effective alternative to surgical intervention with regard to pain reduction. This study aims to assess its long-term effectiveness.

Methods

Patients diagnosed with stage one to three OA received a single intra-articular autologous fat transplantation. Fat tissue was harvested from the abdomen and injected into the trapeziometacarpal (TMC) joint under radiological guidance, followed by one week of immobilization. Patients with a minimum three-year post-procedure period were assessed for pain level (numerical rating scale), quality of life (Mental Health Quotient (MHQ)), the abbreviated version of the Disabilities of Arm, Shoulder and Hand questionnaire (QuickDASH)), and grip and pinch strength, as well as their overall impression of the treatment. Wilcoxon tests compared data from pre-intervention, and at one and three years post-intervention.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 632 - 638
1 Jun 2024
Hart CM Kelley BV Mamouei Z Turkmani A Ralston M Arnold M Bernthal NM Sassoon AA

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

Methods

A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1044 - 1049
1 Oct 2024
Abelleyra Lastoria DA Ogbolu C Olatigbe O Beni R Iftikhar A Hing CB

Aims

To determine whether obesity and malnutrition have a synergistic effect on outcomes from skeletal trauma or elective orthopaedic surgery.

Methods

Electronic databases including MEDLINE, Global Health, Embase, Web of Science, ScienceDirect, and PEDRo were searched up to 14 April 2024, as well as conference proceedings and the reference lists of included studies. Studies were appraised using tools according to study design, including the Oxford Levels of Evidence, the Institute of Health Economics case series quality appraisal checklist, and the CLARITY checklist for cohort studies. Studies were eligible if they reported the effects of combined malnutrition and obesity on outcomes from skeletal trauma or elective orthopaedic surgery.


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.