RESUMEN
Early diagnosis of post-traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high-resolution imaging to investigate early-stage deterioration in articular cartilage and the subchondral bone plate from a sub-critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2- and 14-week post-impact surgery, cartilage-bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (µCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post-impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post-impact, only minor, non-significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2-week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries.
RESUMEN
PURPOSE: Degradation of articular cartilage (AC) due to injury to the knee joint may initiate post-traumatic osteoarthritis (PTOA). Failure to diagnose the onset of the disease at an early stage makes the cure ineffective for PTOA. This study investigated the consequences of a mechanical injury to the knee in a rabbit model using microscopic magnetic resonance imaging (µMRI) at high resolution. MATERIALS AND METHODS: A mechanical injury was induced to the knee joints of 12 rabbits. Cartilage blocks were extracted from the non-impacted and impacted knee joints after 2 and 14 weeks post-impact. The specimens were studied using µMRI T2 relaxation and inductively coupled plasma analysis to determine the early degradation of the articular cartilage. RESULTS: The data established a connection between T2 relaxation time and the early progression of knee PTOA after an impact injury. T2 values were found to be higher in the impacted cartilage at both 2 and 14 weeks, in particular, T2-55° values in the impacted samples displayed a significant rise of 6.93% after 2 weeks and 20.02% after 14 weeks. Lower glycosaminoglycan measurement and higher water content in the impacted cartilage confirmed the µMRI results. CONCLUSIONS: This µMRI T2 study was able to detect cartilage damage in the impacted knees. In addition, greater degradation in the affected knees at 14 weeks than at 2 weeks indicated the progressive nature of cartilage deterioration over time. The µMRI results were in accord with the biochemical analysis, indicating the detection of early structural damage in the cartilage.
Asunto(s)
Cartílago Articular , Osteoartritis , Animales , Conejos , Cartílago Articular/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Modelos Animales de EnfermedadRESUMEN
Traumatized knee greatly contributes to osteoarthritis (OA) of the knee in young adults. To intervene effectively before the onset of severe structural disruption, detection of the disease at the early onset is crucial. In this study, we put together the findings for the detection of OA from the femoral knee joint cartilage of the rabbit at 6 weeks posttrauma. Articular cartilage samples are taken from the impacted and nonimpacted joints at 0 week (serving as the control group) and at 6 weeks posttrauma by minimal force. The samples were imaged using microscopic magnetic resonance imaging (µMRI) at 11.7 µm/pixel and polarized light microscopy (PLM) at 1 µm/pixel. In addition, an inductively coupled plasma - optical emission spectrometry analysis was performed using the adjacent cartilage samples. The outcomes of this study demonstrate an increase in T2 values in 6 weeks samples compared to the 0 week samples by µMRI technique, indicating a general increase of tissue hydration within cartilage. PLM detects a decrease in the average thickness of the superficial zones in the posttraumatic osteoarthritis samples, significant in the impacted femurs. There was an average increasing trend of maximum retardation in the tide mark in comparison to the reported calcium concentration (mg/L) in impacted samples suggesting a possible rise in mineralization in the 6 weeks samples. Qualitatively, physical observation of the joint after 6 weeks showed signs of reddening in the anterior femur suggesting the disease process is a localized phenomenon. Through microscopic imaging, we are able to detect these changes at 6 weeks posttrauma qualitatively and quantitatively.
Asunto(s)
Cartílago Articular , Osteoartritis , Animales , Conejos , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Articulación de la Rodilla/patología , Osteoartritis/patología , Fémur/diagnóstico por imagen , Fémur/patología , Extremidad Inferior , Imagen por Resonancia Magnética/métodosRESUMEN
Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function, and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway, such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goal of this review is to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.