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Bone & Joint Research
Vol. 11, Issue 4 | Pages 189 - 199
13 Apr 2022
Yang Y Li Y Pan Q Bai S Wang H Pan X Ling K Li G

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Methods

A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1442 - 1448
1 Sep 2021
McDonnell JM Evans SR McCarthy L Temperley H Waters C Ahern D Cunniffe G Morris S Synnott K Birch N Butler JS

In recent years, machine learning (ML) and artificial neural networks (ANNs), a particular subset of ML, have been adopted by various areas of healthcare. A number of diagnostic and prognostic algorithms have been designed and implemented across a range of orthopaedic sub-specialties to date, with many positive results. However, the methodology of many of these studies is flawed, and few compare the use of ML with the current approach in clinical practice. Spinal surgery has advanced rapidly over the past three decades, particularly in the areas of implant technology, advanced surgical techniques, biologics, and enhanced recovery protocols. It is therefore regarded an innovative field. Inevitably, spinal surgeons will wish to incorporate ML into their practice should models prove effective in diagnostic or prognostic terms. The purpose of this article is to review published studies that describe the application of neural networks to spinal surgery and which actively compare ANN models to contemporary clinical standards allowing evaluation of their efficacy, accuracy, and relatability. It also explores some of the limitations of the technology, which act to constrain the widespread adoption of neural networks for diagnostic and prognostic use in spinal care. Finally, it describes the necessary considerations should institutions wish to incorporate ANNs into their practices. In doing so, the aim of this review is to provide a practical approach for spinal surgeons to understand the relevant aspects of neural networks.

Cite this article: Bone Joint J 2021;103-B(9):1442–1448.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 668 - 676
1 Oct 2021
Liu L Li Z Chen S Cui H Li X Dai G Zhong F Hao W Zhang K Liu H

Aims

Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy.

Methods

Achilles tendon puncture (ATP) mouse model was performed on ten-week-old male C57BL/6J mice. One week after ATP procedure, the mice were given different treatments (e.g. JQ1, shMancr). Achilles tendon samples were collected five weeks after treatment for RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) analysis; the legs were removed for micro-CT imaging and subsequent histology. Human bone marrow mesenchymal stem cells (hBMSCs) were isolated and purified bone marrow collected during surgeries by using density gradient centrifugation. After a series of interventions such as knockdown or overexpressing BRD4, Alizarin red staining, RT-qPCR, and Western Blot (Runx2, alkaline phosphatase (ALP), Osx) were performed on hBMSCs.


Bone & Joint 360
Vol. 11, Issue 1 | Pages 21 - 22
1 Feb 2022


Bone & Joint Research
Vol. 11, Issue 2 | Pages 73 - 81
22 Feb 2022
Gao T Lin J Wei H Bao B Zhu H Zheng X

Aims

Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive.

Methods

We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli.


Bone & Joint Open
Vol. 3, Issue 2 | Pages 123 - 129
1 Feb 2022
Bernard J Bishop T Herzog J Haleem S Lupu C Ajayi B Lui DF

Aims

Vertebral body tethering (VBT) is a non-fusion technique to correct scoliosis. It allows correction of scoliosis through growth modulation (GM) by tethering the convex side to allow concave unrestricted growth similar to the hemiepiphysiodesis concept. The other modality is anterior scoliosis correction (ASC) where the tether is able to perform most of the correction immediately where limited growth is expected.

Methods

We conducted a retrospective analysis of clinical and radiological data of 20 patients aged between 9 and 17 years old, (with a 19 female: 1 male ratio) between January 2014 to December 2016 with a mean five-year follow-up (4 to 7).


Bone & Joint 360
Vol. 10, Issue 3 | Pages 4 - 5
1 Jun 2021
Page PRJ Poole WEC Handley R


Bone & Joint Open
Vol. 3, Issue 1 | Pages 93 - 97
10 Jan 2022
Kunze KN Orr M Krebs V Bhandari M Piuzzi NS

Artificial intelligence and machine-learning analytics have gained extensive popularity in recent years due to their clinically relevant applications. A wide range of proof-of-concept studies have demonstrated the ability of these analyses to personalize risk prediction, detect implant specifics from imaging, and monitor and assess patient movement and recovery. Though these applications are exciting and could potentially influence practice, it is imperative to understand when these analyses are indicated and where the data are derived from, prior to investing resources and confidence into the results and conclusions. In this article, we review the current benefits and potential limitations of machine-learning for the orthopaedic surgeon with a specific emphasis on data quality.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 437 - 444
27 Jul 2021
Yan F Feng J Yang L Shi C

Aims

The aim of our study is to investigate the effect induced by alternated mechanical loading on Notch-1 in mandibular condylar cartilage (MCC) of growing rabbits.

Methods

A total of 64 ten-day-old rabbits were randomly divided into two groups according to dietary hardness: normal diet group (pellet) and soft diet group (powder). In each group, the rabbits were further divided into four subgroups by feeding time: two weeks, four weeks, six weeks, and eight weeks. Animals would be injected 5-bromo-2′-deoxyuridine (BrdU) every day for one week before sacrificing. Histomorphometric analysis of MCC thickness was performed through haematoxylin and eosin (HE) staining. Immunochemical analysis was done to test BrdU and Notch-1. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to measure expression of Notch-1, Jagged-1, and Delta-like 1 (Dll-1).


Aims

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing.

Methods

A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.


Bone & Joint Research
Vol. 11, Issue 1 | Pages 40 - 48
27 Jan 2022
Liao W Sun J Wang Y He Y Su K Lu Y Liao G Sun Y

Aims

In the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism.

Methods

SMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated.


Bone & Joint Research
Vol. 10, Issue 8 | Pages 526 - 535
1 Aug 2021
Xin W Yuan S Wang B Qian Q Chen Y

Aims

Circular RNAs (circRNAs) are a novel type of non-coding RNA that plays major roles in the development of diverse diseases including osteonecrosis of the femoral head (ONFH). Here, we explored the impact of hsa_circ_0066523 derived from forkhead box P1 (FOXP1) (also called circFOXP1) on bone mesenchymal stem cells (BMSCs), which is important for ONFH development.

Methods

RNA or protein expression in BMSCs was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot, respectively. Cell Counting Kit 8 (CCK8) and 5-ethynyl-2’-deoxyuridine (EdU) were used to analyze cell proliferation. Alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red S staining were employed to evaluate the osteoblastic differentiation. Chromatin immunoprecipitation (ChIP), luciferase reporter, RNA pull down, and RNA immunoprecipitation (RIP) assays were combined for exploring molecular associations.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 459 - 466
28 Jul 2021
Yang J Zhou Y Liang X Jing B Zhao Z

Aims

Osteoarthritis (OA) is characterized by persistent destruction of articular cartilage. It has been found that microRNAs (miRNAs) are closely related to the occurrence and development of OA. The purpose of the present study was to investigate the mechanism of miR-486 in the development and progression of OA.

Methods

The expression levels of miR-486 in cartilage were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN), matrix metalloproteinase (MMP)-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) in SW1353 cells at both messenger RNA (mRNA) and protein levels was determined by qRT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Double luciferase reporter gene assay, qRT-PCR, and western blot assay were used to determine whether silencing information regulator 6 (SIRT6) was involved in miR-486 induction of chondrocyte-like cells to a more catabolic phenotype.


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1319 - 1324
1 Oct 2014
Oh JS Youm YS Cho SD Choi SW Cho YJ

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors. Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA. Cite this article: Bone Joint J 2014;96-B:1319–24


Bone & Joint Research
Vol. 10, Issue 10 | Pages 693 - 703
1 Oct 2021
Wang X Wang D Xia P Cheng K Wang Q Wang X Lin Q Song J Chen A Li X

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMDSV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Methods

In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDSV on alternate days for four weeks. Chondrocytes were also treated with PPARγ inhibitor, PPARγ inhibitor+ UTMDSV, and UTMDSV. The cholesterol efflux rate and triglyceride levels were measured using an assay kit and oil red O staining, respectively. In vivo, the OA rabbits were treated with a single intra-articular injection of UTMD, SV, and UTMDSV every seven days for four weeks. Cartilage histopathology was assessed by safranin-O staining and the Mankin score. Total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by enzyme-marker assay. Aggrecan, collagen II, and PPARγ expression levels were analyzed by Western blotting (WB).


Bone & Joint Research
Vol. 10, Issue 10 | Pages 677 - 689
1 Oct 2021
Tamaddon M Blunn G Xu W Alemán Domínguez ME Monzón M Donaldson J Skinner J Arnett TR Wang L Liu C

Aims

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Methods

The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 767 - 779
8 Dec 2021
Li Y Yang Y Wang M Zhang X Bai S Lu X Li Y Waldorff EI Zhang N Lee WY Li G

Aims

Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.

Methods

The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation.


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1553 - 1554
1 Oct 2021
Haddad FS


Bone & Joint Research
Vol. 10, Issue 2 | Pages 122 - 133
1 Feb 2021
He CP Jiang XC Chen C Zhang HB Cao WD Wu Q Ma C

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2021;10(2):122–133.


Bone & Joint Open
Vol. 2, Issue 11 | Pages 909 - 920
10 Nov 2021
Smith T Clark L Khoury R Man M Hanson S Welsh A Clark A Hopewell S Pfeiffer K Logan P Crotty M Costa M Lamb SE

Aims

This study aims to assess the feasibility of conducting a pragmatic, multicentre randomized controlled trial (RCT) to test the clinical and cost-effectiveness of an informal caregiver training programme to support the recovery of people following hip fracture surgery.

Methods

This will be a mixed-methods feasibility RCT, recruiting 60 patients following hip fracture surgery and their informal caregivers. Patients will be randomized to usual NHS care, versus usual NHS care plus a caregiver-patient dyad training programme (HIP HELPER). This programme will comprise of three, one-hour, one-to-one training sessions for the patient and caregiver, delivered by a nurse, physiotherapist, or occupational therapist. Training will be delivered in the hospital setting pre-patient discharge. It will include practical skills for rehabilitation such as: transfers and walking; recovery goal setting and expectations; pacing and stress management techniques; and introduction to the HIP HELPER Caregiver Workbook, which provides information on recovery, exercises, worksheets, and goal-setting plans to facilitate a ‘good’ recovery. After discharge, patients and caregivers will be supported in delivering rehabilitation through three telephone coaching sessions. Data, collected at baseline and four months post-randomization, will include: screening logs, intervention logs, fidelity checklists, quality assurance monitoring visit data, and clinical outcomes assessing quality of life, physical, emotional, adverse events, and resource use outcomes. The acceptability of the study intervention and RCT design will be explored through qualitative methods with 20 participants (patients and informal caregivers) and 12 health professionals.