Journal of Orthopaedic Research®最新文献

There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra-articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra-articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6-month-old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center-edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real-time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C-KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI.

Extracellular vesicles (EVs) derived from endometrial-derived mesenchymal stem/stromal cells (eMSC) play a crucial role in tissue repair due to their immunomodulatory and reparative properties. Given these properties, eMSC EVs may offer potential benefits for meniscal repair. The meniscus, being partly vascularized, relies on diffusivity for solute trafficking. This study focuses on EVs transport properties characterization within fibrocartilage that remains unknown. Specifically, EVs were isolated from Crude and CD146⁺ eMSC populations. Green fluorescence-labeled EVs transport properties were investigated in three structurally distinct layers (core, femoral, and tibial surfaces) of porcine meniscus. Diffusivity was measured via custom fluorescence recovery after photobleaching (FRAP) technique. Light spectrometry was used to determine EVs solubility. Both Crude and CD146⁺ eMSC EVs exhibited high purity (>90% CD63CD9 marker expression) and an average diffusivity of 10.924 (±4.065) µm²/s. Importantly, no significant difference was observed between Crude and CD146⁺ eMSC EV diffusivity on the meniscal layer (p > 0.05). The mean partitioning coefficient was 0.2118 (±0.1321), with Crude EVs demonstrating significantly higher solubility than CD146⁺ EVs (p < 0.05). In conclusion, this study underscores the potential of both Crude and CD146⁺ eMSC EVs to traverse all layers of the meniscus, supporting their capacity to enhance delivery of orthobiologics for cartilaginous tissue healing.

Osteoarthritis is a degenerative disease of synovial joints affecting all tissues, including articular cartilage and subchondral bone. Osteoarthritis animal models can recapitulate aspects of human disease progression and are used to test efficacy of drugs, biomaterials, and cell therapies. The rat medial meniscus transection (MMT) model is a surgically induced posttraumatic osteoarthritis model commonly used for preclinical therapeutic screening. We describe herein, the qualitative and quantitative changes to articular cartilage, subchondral bone, and formation of osteophytes at early-, mid-, and late-stages of osteoarthritis progression. Tibia of MMT-operated animals showed proteoglycan loss and fibrillation along articular cartilage surfaces as early as 3-weeks post-surgery. With contrast-enhanced micro-CT technique, quantitative, 3-dimensional analysis of the tibia showed that the articular cartilage thickened at 3- and 6-weeks post-surgery and decreased at 12-weeks post-surgery. This decreased cartilage thickness corresponded with increased lesions in the articular cartilage that led to its full degradation and exposing the subchondral bone layer. Further, subchondral bone thickening was significant at 6-weeks post-surgery and followed cartilage damage. Osteophytes were found as early as 3-weeks post-surgery and coincided with articular cartilage degradation. Cartilaginous osteophytes preceded mineralization, suggesting endochondral ossification. The rat MMT model has predominantly been used out to 3-weeks, and most studies determined the effect of therapies to delay or prevent the onset of osteoarthritis. We provide evidence that an extension of the rat MMT model out to 6- and 12-weeks more resembled severe phenotypes of human osteoarthritis. Thus, evaluating novel therapeutics at late-stage will be important for eventual clinical translation.

End-stage ankle arthritis is often treated surgically by total ankle arthroplasty (TAA) due to its potential to improve gait through increased joint range of motion and reduce pain. However, TAA's effect on gait stability is not well understood. This study explores the impact of TAA on gait stability, measured by Margin of Stability (MoS), in 148 patients with end-stage ankle arthritis. Kinematic data were collected pre-operatively, at 1-year post-op, and at 2-years post-op and the MoS was determined at heel strike and midstance for the anteroposterior (MoS_AP) and mediolateral (MoS_ML) directions. A linear mixed effects model including gait speed as a factor was used to assess the effects of limb, session, and their interaction on outcome measures. A significant interaction (p < 0.002) between limb (surgical, nonsurgical) and session (pre-op, 1-year post-op, 2-years post-op) was identified for each MoS variable of interest. Cumulatively, our results suggest that the nonsurgical limb, MoS_AP at heel strike and MoS_ML at midstance improved (increased) as time from surgery increased. These results suggest patients developed a compensatory movement pattern to navigate surgical limb single support. TAA reduces this compensation improving side-to-side symmetry, while not fully restoring symmetry by 2-years post-op. These results indicate that TAA could improve gait stability in patients with end-stage ankle arthritis, but further work is needed to understand the impact of TAA on altering fall risk.

Staphylococcus aureus has multiple mechanisms to evade the host's immune system and antibiotic treatment. One such mechanism is the invasion of the osteocyte lacuno-canalicular network (OLCN), which may be particularly important in recurrence of infection after debridement and antibiotic therapy. The aim of this study was to develop an ex vivo model to facilitate further study of S. aureus invasion of the OLCN and early-stage testing of antibacterial strategies against bacteria in this niche. The diameter of the canaliculi of non-infected human, sheep, and mouse bones was measured microscopically on Schmorl's picrothionin stained sections, showing a large overlap in canalicular diameter. S. aureus successfully invaded the OLCN in all species in vitro as revealed by presence in osteocyte lacunae in Brown and Brenn-stained sections and by scanning electron microscopy. Murine bones were then selected for further experiments, and titanium pins with either a wild-type or ΔPBP4 mutant S. aureus USA300 were placed trans-cortically and incubated for 2 weeks in tryptic soy broth. Wild-type S. aureus readily invaded the osteocyte lacunae in mouse bones while the ΔPBP4 showed a significantly lower invasion of the OLCN (p = 0.0005). Bone specimens were then treated with gentamicin, sitafloxacin, R14 bacteriophages, or left untreated. Gentamicin (p = 0.0027) and sitafloxacin (p = 0.0280) significantly reduced the proportion of S. aureus-occupied lacunae, whilst bacteriophage treatment had no effect. This study shows that S. aureus is able to invade the OLCN in an ex vivo model. This ex vivo model can be used for future early-stage studies before proceeding to in vivo studies.

te Moller NCR, Mohammadi A, Plomp S, et al. Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9-month equine groove model study. J Orthop Res.2021;39:2363–2375.

In the supporting information document jor24971-sup-0007-Supplementary_Material-EquineGrooveModel_12-2020.pdf, on page 22, the Supplementary data set is mentioned: “Data generated by this research and used for analysis in the current paper, will be made available from data repository.” The link to this data set was missing. The data can be accessed via the link below:

https://public.yoda.uu.nl/dgk/UU01/0TO6PE.html

And has the following persistent identifier:

doi:10.24416/UU01-0TO6PE

We apologize for the delay.

Flatfoot, a foot deformity characterized by the collapse of the arch, significantly impacts an individual's balance and stability. This study explored postural adjustments and sway excursions in individuals with and without flatfoot using the Time-in-Boundary method. This method assessed relative stability by exploring various center of pressure radius thresholds during three trials of single-leg stance. We observed significant interactions in threshold levels (F = 4.37, p = 0.04) and normalized relative stable times (F = 7.64, p = 0.01), particularly in the initial trials. Initially, the flatfoot group showed marked decreases in stable times at 10 mm, 15 mm, and 20 mm thresholds, which expanded to 25 mm and 30 mm in subsequent trials. Despite a significant decrease in stability at the 30 mm threshold in early trials, participants exhibited improved stability control as trials progressed. This enhancement likely reflects a combination of a learning effect and an increased understanding of the task requirements, underscoring the adaptability of postural control systems to the biomechanical challenges posed by flatfoot. The Time-in-Boundary method has proven to be an effective tool for clinicians to assess postural control, playing a vital role in developing customized rehabilitation strategies for individuals with flatfoot.