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). Results. In vitro, UTMDSV significantly increased the cholesterol efflux rate and aggrecan, collagen II, and PPARγ levels in OA chondrocytes; these effects were blocked by the PPARγ inhibitor. In vivo, UTMD. SV. significantly increased aggrecan, collagen II, PPARγ, and HDL-C levels, while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA, and control groups. Conclusion. UTMDSV promotes cartilage extracellular matrix synthesis by modulating the PPARγ-mediated cholesterol efflux pathway in OA rabbits. Cite this article: Bone Joint Res 2021;10(10):693–703

Aims. Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Methods. High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. Results. More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-β1) was downregulated, while that of TGF-β2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. Conclusion. DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558–570

Gluteal Tendinopathy is a poorly understood condition that predominantly affects post-menopausal women. It causes lateral hip pain, worse when lying on the affected side or when walking up a hill or stairs. It has been labelled ˜Greater Trochanteric Pain Syndrome” a name that recognises the lack of understanding of the condition. Surgical reconstruction of the gluteal cuff is well established and has been undertaken numerous times over the last 16 years by the senior author (AJL). However, the quality of collagen in the tendons can be very poor and this leads to compromised results. We present the results of gluteal cuff reconstruction combined with augmentation using a bioinductive implant. 14 patients (11 female, 3 male; mean age 74.2 ± 6.3 years) with significant symptoms secondary to gluteal tendinopathy that had failed conservative treatment (ultrasound guided injection and structured physiotherapy) underwent surgical reconstruction by the senior author using an open approach. In all cases the iliotibial band was lengthened and the trochanteric bursa excised. The gluteal cuff was reattached using Healicoil anchors (3–5×4.75mm anchors; single anchors but double row repair) and then augmented using a Regeneten patch. Patients were mobilised fully weight bearing post-operatively but were asked to use crutches until they were no longer limping. All had structured post-surgery rehabilitation courtesy of trained physiotherapists. There were no post-operative complications and all patients reported an improvement in pain levels (Visual Analogue Scale 7.8 pre-op; 2.6 post-op) and functional levels (UCLA Activity Score 3.5 pre-op; 7.1 post-op) at 6 months post surgery. Surgery for gluteal tendinopathy produces good outcomes and the use of Regeneten as an augment for poor quality collagen is seemingly a safe, helpful addition. Further comparative studies would help clarify this

Hypermobility Spectrum Disorder (HSD or hEDS) is attributed to a collagen abnormality associated with excessive joint flexibility. Approximately 90% of females with hip dysplasia have hypermobility. Manifestations of hypermobility in various body systems are unique to every patient, affecting different tissues of the body with varying degrees of severity. Our purposes were to identify the manifestations of hypermobility across multiple body systems and to study the recognition of hypermobility in the medical literature of multiple specialties over multiple decades. A literature search of the major medical disciplines for key words associated with HSD was performed. These specialties included gastroenterology, gynecology, neurology, psychiatry, oral-maxillofacial surgery, cardiology, and orthopaedic surgery. A specialty-specific impact factor (IF) score was calculated as the percentage of research articles that referenced hypermobility as a comorbidity over all articles within that specialty. Statistical differences were identified using single factor ANOVA with significance determined at p<0.05. We reviewed many published, specialty-specific manifestations of hypermobility, and describe them. All six non-orthopaedic specialties demonstrated a continually increasing relative IF ratio throughout the study period with a peak impact average of 0.22 (p<0.05 compared with other time ranges). There was a 93.3% overall increase in IF scores from the 1992–1998 period to the most recent period examined (p<0.05). Hypermobility is increasingly recognized as a significant health issue in multiple disciplines. Since dysplasia is associated with approximately 40% of all primary total hip arthroplasty cases, understanding the multi-system manifestations, and broad impact of hypermobility on patients, is relevant for every hip surgeon. We are expanding our research into other medical disciplines, including urology, ophthalmology, dermatology, clinical psychology, and others

Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results. Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion. Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513

Objectives. The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1). Methods. A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR (qRT-PCR) was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL1), type 2 collagen (COL2), SRY-related high mobility group-box gene9 (SOX9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase 13 (MMP-13). Expression of related proteins was detected by Western blotting. Results. The current study showed that CTGF could promote the recovery of an injured anterior cruciate ligament. It can upregulate mRNA and expression of TGF-β1, COL1, COL2, SOX9, and tissue inhibitor of TIMP-1, and downregulate mRNA and expression of MMP-13, suggesting that the curative effect of CTGF on injured rabbit ligaments is through regulation of these cellular factors. Conclusions. This finding revealed the healing role of CTGF in injured tissues and provides new possibilities of treating injured tissues and wound healing by using CTGF. Cite this article: X. Sun, W. Liu, G. Cheng, X. Qu, H. Bi, Z. Cao, Q. Yu. The influence of connective tissue growth factor on rabbit ligament injury repair. Bone Joint Res 2017;6:399–404. DOI: 10.1302/2046-3758.67.BJR.2016-0255.R1

Background. Structural bone allografts are an established treatment method for long-bone structural defects arising from such conditions as trauma, sarcoma, and osteolysis following total joint replacement. However, the quality of structural bone allografts is difficult to non-destructively assess prior to use. The functional lifetime of structural allografts depend on their ability to resist cyclic loading, which can lead to fracture even at stress levels well below the yield strength. Because allograft bone has limited capacity for remodeling, optimizing allograft selection for bone quality could decrease long-term fracture risk. Raman spectroscopy biomarkers can non-destructively assess the three primary components of bone (collagen, mineral, and water), and may predict the resistance of donor bone allografts to fracture from cyclic loads. The purpose of this study was to prospectively assess the ability of Raman biomarkers to predict number of cycles to fracture (“cyclic fatigue life”) of human allograft cortical bone. Methods. Twenty-one cortical bone specimens were from the mid-diaphysis of human donor bone tissue (bilateral femurs from 4 donors: 63M, 61M, 51F, 48F) obtained from the Musculoskeletal Transplant Foundation. Six Raman biomarkers were analyzed: collagen disorganization, type B carbonate substitution (a surrogate for mineral maturation), matrix mineralization, and 3 water compartments. Specimens underwent cyclic fatigue testing under fully reversed conditions at 35 and 45MPa (physiologically relevant stress levels for structural allografts). Specimens were tested to fracture or to 30 million cycles (“run-out”), simulating 15 years of moderate activity (i.e., 6000 steps per day). Multivariate regression analysis was performed using a tobit model (censored linear regression) for prediction of cyclic fatigue life. Specimens were right-censored at 30 million cycles. Results. All of the 6 biomarkers that were evaluated were independently associated with cyclic fatigue life (p < 0.05). The multivariate model explained 70% of the variance in cyclic fatigue life (R2=0.695, p<0.001,). Increasing disordered collagen (p<0.001) and loosely collagen-bound water compartments (p<0.001) were associated with decreased cyclic fatigue life. Increasing type B carbonate substitution (p<0.001), matrix mineralization (p<0.001), tightly collagen-bound water (p<0.001), and mineral-bound water (p=0.002) were associated with increased cyclic fatigue life. In the predictive model, 42% of variance in cyclic fatigue life was attributable to degree of collagen disorder, all bound water compartments accounted for 6%, and age and sex accounted for 17%. Conclusions. Raman biomarkers of three bone components (collagen, mineral, and water) predict cyclic fatigue life of human cortical bone. Increased baseline collagen disorder was associated with decreased cyclic fatigue life, and was the strongest determinant of cyclic fatigue life. Increased matrix mineralization and mineral maturation were associated with increased cyclic fatigue life. Bound-water compartments of bone contributed minimally to cyclic fatigue life. These results are complementary with prior Raman studies of monotonic testing of bone that reported decreased toughness and strength with increased collagen disorder and increased stiffness with increased bone mineralization and mineral maturation. This model should be prospectively validated. Raman analysis is a promising tool for the non-destructive evaluation of structural bone allograft quality and may be useful as a screening tool for selection of allograft bone. Acknowledgements. Supported by a grant from the Musculoskeletal Transplant Foundation. The Dudley P. Allen Fellowship (JYD), Wilbert J. Austin Professor of Engineering Chair (CMR) and the Leonard Case Jr. Professor of Engineering Chair (OA) are gratefully acknowledged

In developmental dysplasia of the hip, a deficient acetabulum may be augmented by placing local autogenous iliac osseous graft, or the ilium itself, over the head of the femur with the expectation that the added bone will function as a bearing surface. We analysed this bone obtained en bloc during subsequent surgery which was performed for degenerative osteoarthritis in three patients at 6, 25 and 30 years after the initial augmentation procedure. In each patient, the augmentation comprised of red cancellous bone covered on its articulating surface by a distinct layer of white tissue. Microscopy of this tissue showed parallel rows of spindle-shaped cells lying between linearly arranged collagen bundles typical of joint capsule. Biochemical analysis showed type I collagen, the principal collagen of joint capsule and bone, with no significant quantity of type II collagen, the principal collagen of cartilage. While the added bone produced by acetabular augmentation was durable, histological and biochemical analyses suggested that it had not undergone cartilage metaplasia. The augmented acetabulum articulates with the head of the femur by means of an interposed hip joint capsule

Aims

A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach.

Damage to and repair of the acetabular labral-chondral complex are areas of clinical interest in the treatment of young adults with pain in the hip and in the prevention of degenerative arthritis of the hip. There are varying theories as to why most acetabular tears are located anterosuperiorly. We have studied the prenatal development of the human acetabular labral-chondral complex in 11 fetal hips, aged from eight weeks of gestation to term. There were consistent differences between the anterior and posterior acetabular labral-chondral complex throughout all ages of gestation. The anterior labrum had a somewhat marginal attachment to the acetabular cartilage with an intra-articular projection. The posterior labrum was attached and continuous with the acetabular cartilage. Anteriorly, the labral-chondral transition zone was sharp and abrupt, but posteriorly it was gradual and interdigitated. The collagen fibres of the anterior labrum were arranged parallel to the labral-chondral junction, but at the posterior labrum they were aligned perpendicular to the junction. We believe that in the anterior labrum the marginal attachment and the orientation of the collagen fibres parallel to the labral-chondral junction may render it more prone to damage than the posterior labrum in which the collagen fibres are anchored in the acetabular cartilage. The anterior intra-articular projection of the labrum should not be considered to be a pathological feature

Aims

Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI.

Aims

Pelvic incidence (PI) is considered an important anatomical parameter for determining the sagittal balance of the spine. The contribution of an abnormal PI to hip osteoarthritis (OA) remains controversial. In this study, we aimed to investigate the relationship between PI and hip OA, and the difference in PI between hip OA without anatomical abnormalities (primary OA) and hip OA with developmental dysplasia of the hip (DDH-OA).

Background. Heterotopic ossification (HO) is lamellar bone formation in the soft tissues following trauma or joint replacement for osteoarthritis (OA). A genome wide association study of HO patients after total hip arthroplasty for OA has identified Kinesin Family Member 26B (KIF26B) as a gene associated with HO severity. KIF26B has previously been associated with HO in mice. Hypothesis and aims: We hypothesised that Kif26b regulates the osteogenic trans-differentiation of myoblasts; a possible mechanism of HO. Using an in vitro model, we wished to establish whether Kif26b is involved in HO formation and to explore the molecular mechanism. Methods. We developed CRISPR/Cas9 mediated Kif26b knockout (KO) C2C12 myoblasts. Wild type (WT) and KO cells were transdifferentiated towards an osteogenic lineage using BMP-2 for 24 days. The effect of Kif26b KO on mineralisation was quantified by calcium staining. The mean difference (±SEM) in gene expression between WT and KO lines was compared with ANOVA. Results. qPCR and western blotting confirmed Kif26b knockout. Kif26b deficient cells produced substantially less mineral versus WT in response to BMP-2 (34.71% ±3.62%, n=12, P<0.0001). At day 8 of osteogenic differentiation, loss of Kif26b abrogated Osterix (113.6 ±6.781 n=5, P<0.0001), Osteocalcin (737.9 ±84.25, n=5, P<0.0001) and Alkaline phosphatase (6989 ±365.7, n=5, P<0.0001) expression, and down regulated Runx2 (2.725 ±0.7724, n=5, P<0.0052) and Collagen type I (7.25 ±1.154, n=5, P<0.0001) expression relative to WT. The knockout cells also appeared morphologically different. Compared to WT, the Kif26b KO cells displayed a less osteoblast-like morphology during transdifferentiation. Conclusion. Our findings demonstrate an undescribed function for Kif26b as a critical regulator of pathological ossification, with a putative role in HO pathogenesis after THA

Aims

The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants.

Aims

The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

Aims

The aims of this study were to assess the exposure and preservation of the abductor mechanism during primary total hip arthroplasty (THA) using the posterior approach, and to evaluate gluteus maximus transfer to restore abductor function of chronically avulsed gluteus medius and minimus.

Aims

Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs.

Objectives

Legg–Calvé–Perthes’ disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition.

Aims

Many case reports and small studies have suggested that cobalt ions are a potential cause of cardiac complications, specifically cardiomyopathy, after metal-on-metal (MoM) total hip arthroplasty (THA). The impact of metal ions on the incidence of cardiac disease after MoM THA has not been evaluated in large studies. The aim of this study was to compare the rate of onset of new cardiac symptoms in patients who have undergone MoM THA with those who have undergone metal-on-polyethylene (MoP) THA.

The acetabular labrum is a soft-tissue structure which lines the acetabular rim of the hip joint. Its role in hip joint biomechanics and joint health has been of particular interest over the past decade. In normal hip joint biomechanics, the labrum is crucial in retaining a layer of pressurised intra-articular fluid for joint lubrication and load support/distribution. Its seal around the femoral head is further regarded as a contributing to hip stability through its suction effect. The labrum itself is also important in increasing contact area thereby reducing contact stress. Given the labrum’s role in normal hip joint biomechanics, surgical techniques for managing labral damage are continuously evolving as our understanding of its anatomy and function continue to progress. The current paper aims to review the anatomy and biomechanical function of the labrum and how they are affected by differing surgical techniques.

Take home message: The acetabular labrum plays a critical role in hip function and maintaining and restoring its function during surgical intervention remain an essential goal.

Cite this article: Bone Joint J 2016;98-B:730–5.