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

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

Introduction. In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits. Methods. Thirty-six male skeletally mature NZW rabbits received methylprednisolone acetate (20mg/kg) IM once 4 weeks before surgery. There were 6 groups:. CD alone – a 3 mm drill hole. + injection into the CD of:. hydrogel (HG) - 200 μl of hydrogel carrier. MSCs–1 million rabbit MSCs. pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs. IL4-MSCs – rabbit IL-4 over-expressing MSCs. IL4-pMSCs – preconditioned IL-4 over-expressing MSCs. Eight weeks after surgery, femurs were harvested, and evaluated by microCT, biomechanical, and histological analyses. Results. Bone mineral density (BMD) and bone volume fraction (BVF) increased in the pMSC group compared to the CD and MSC groups . outside. of the CD area (p < 0.05, Fig.1). Similarly, the IL4-pMSC group was increased compared to the CD group (p < 0.05). The percentage of empty lacunae in the IL4-MSC group was significantly less than other groups . outside. the CD area (p < 0.05, Fig.2); however, IL4-MSC group had less trabecular bone formation . inside. the CD. The mechanical tests demonstrated no differences. Discussion. This rabbit steroid-associated ONFH model demonstrated that pMSC increased new bone formation after CD; IL4-MSCs that continuously secreted IL-4 decreased the number of empty lacunae . Immunomodulation of bone healing has the potential to improve bone healing after CD for early stage ONFH; these interventions must be applied in a temporally sensitive fashion. For any figures, tables, or references, please contact the authors directly

The gold standard for PJI treatment comprises the use of antibiotic-loaded bone cement spacers, which are limited in their load bearing capacity[1]. Thus, developing an antibiotic-eluting UHMWPE bearing surface can improve the mechanical properties of spacers and improve the quality of life of PJI patients. In this study, we incorporated vancomycin into UHMWPE to investigate its elution characteristics, mechanical properties and its efficacy against an acute PJI in an animal model. Vancomycin hydrochloride was incorporated into UHMWPE (2 to 14%) by blending and consolidation. We studied drug elution with blocks in PBS and UV-Vis spectroscopy at 280 nm. We determined the tensile mechanical properties and impact strength [3]. We implanted osteochondral plugs in rabbits using either control UHMWPE, bone cement (40g) containing vancomycin (1g) and tobramycin (3.6g) or vancomycin-eluting UHMWPE (n=5) plugs in the patellofemoral groove of rabbits. All rabbits received a beaded titanium rod in the tibial canal. All groups received two doses of 5×10. 7. cfu of bioluminescent S. aureus in the distal tibial canal prior to insertion of the rod and the articular space after closure of the joint capsule. No intravenous antibiotics were used. Bioluminescence signal was measured when the rabbits expired, or at 21-day post-op. Hardware, polyethylene implants, and joint tissues were sonicated to further quantify live bacteria via plate seeding. Vancomycin elution increased with increasing drug loading. Vancomycin elution above MIC for 3 weeks and optimized mechanical properties were obtained at 6–7 wt% vancomycin loading in UHMWPE. In our lapine acute infection model using bioluminescent S. aureus, knees treated with UHMWPE without antibiotics and bone cement containing vancomycin and tobramycin had significantly higher bioluminescence compared to those treated with vancomycin-eluting UHMWPE. These results suggest that an antibiotic-eluting UHMWPE spacer with acceptable properties as a bearing surface could be used to treat periprosthetic joint infection in lieu of bone cement spacers and this could allow safer load bearing and a higher quality of life for the patients during treatment. In addition, this presents a safer alternative in cases where the second stage surgery for the implantation of new components is hindered

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.

Aims

The purpose of this study was to evaluate the biological fixation of a 3D printed porous implant, with and without different hydroxyapatite (HA) coatings, in a canine model.

Objectives

The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models.

Our understanding of the origin of hip pain in degenerative disorders of the hip, including primary osteoarthritis, avascular necrosis and femoroacetabular impingement (FAI), is limited. We undertook a histological investigation of the nociceptive innervation of the acetabular labrum, ligamentum teres and capsule of the hip, in order to prove pain- and proprioceptive-associated marker expression. These structures were isolated from 57 patients who had undergone elective hip surgery (44 labral samples, 33 ligamentum teres specimens, 34 capsular samples; in 19 patients all three structures were harvested). A total of 15 000 histological sections were prepared that were investigated immunohistochemically for the presence of protein S-100, 68 kDa neurofilament, neuropeptide Y, nociceptin and substance P. The tissues were evaluated in six representative areas.

Within the labrum, pain-associated free nerve ending expression was located predominantly at its base, decreasing in the periphery. In contrast, the distribution within the ligamentum teres showed a high local concentration in the centre. The hip capsule had an almost homogeneous marker expression in all investigated areas.

This study showed characteristic distribution profiles of nociceptive and pain-related nerve fibres, which may help in understanding the origin of hip pain.

Cite this article: Bone Joint J 2013;95-B:770–6.

The cause of fracture of the femoral neck after hip resurfacing is poorly understood. In order to evaluate the role of avascular necrosis we compared 19 femoral heads retrieved at revision for fracture of the femoral neck and 13 retrieved for other reasons.

We developed a new technique of assessing avascular necrosis in the femoral head by determining the percentage of empty osteocyte lacunae present. Femoral heads retrieved as controls at total hip replacement for osteoarthritis and avascular necrosis had 9% (sd 4; n = 13) and 85% (sd 5; n = 10, p < 0.001) empty lacunae, respectively.

In the fracture group the percentage of empty lacunae was 71% (sd 22); in the other group it was 21% (sd 13). The differences between the groups were highly significant (p < 0.001).

We conclude that fracture after resurfacing of the hip is associated with a significantly greater percentage of empty osteocyte lacunae within the trabecular bone. This indicates established avascular necrosis and suggests that damage to the blood supply at the time of surgery is a potent risk factor for fracture of the femoral neck after hip resurfacing.

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.