Inflammatory events in cartilage in early stages of femoroacetabular impingement: Commentary on an article by Shingo Hashimoto, MD, PhD, et al.: "Molecular characterization of articular cartilage from young adults with femoroacetabular impingement".
Inflammatory events in cartilage in early stages of femoroacetabular impingement: Commentary on an article by Shingo Hashimoto, MD, PhD, et al.: "Molecular characterization of articular cartilage from young adults with femoroacetabular impingement".
Project description:The concept of femoroacetabular impingement syndrome (FAIS) has received much attention over the past 20 years. Currently, it is believed that FAIS can lead to intra-articular pathologies such as labral tears and articular cartilage lesions, resulting in clinical symptoms and subsequent poor clinical outcomes. FAIS-related articular cartilage lesions are common but unique, and their natural course always leads to early osteoarthritis of the hip. However, despite these cartilage lesions having gradually gained considerable attention, limited consensus has been reached on key aspects, such as diagnosis, mechanisms, classification, and management strategies, which limits clinical and research advances. Hence, an intensive comprehensive overview based on the existing evidence is necessary. The purpose of this review was to introduce the general consensus, controversial issues, and recent advances in FAIS-related articular cartilage lesions.
Project description:BackgroundFemoroacetabular impingement is a frequent cause of hip pain and may lead to secondary osteoarthritis, yet little is known about the molecular events linking mechanical hip impingement and articular cartilage degeneration. The first goal of this study was to quantify the expression of inflammatory cytokine and chemokine, matrix-degrading, and extracellular matrix genes in articular cartilage harvested from control hips and hips with femoroacetabular impingement and end-stage osteoarthritis. The second goal was to analyze the relative expression of these genes in articular cartilage harvested at various stages of osteoarthritis.MethodsCartilage samples were obtained from thirty-two hips undergoing hip preservation surgery for femoroacetabular impingement or hip arthroplasty. Three control cartilage samples were also analyzed. Specimens were graded intraoperatively with regard to the severity of cartilage damage, the radiographic osteoarthritis grade was recorded, and quantitative RT-PCR (real-time polymerase chain reaction) was performed to determine relative gene expression.ResultsExcept for interleukin-1β (IL-1β) and CXCL2, the mRNA (messenger RNA) expression of all other chemokine (IL-8, CXCL1, CXCL3, CXCL6, CCL3, and CCL3L1), matrix-degrading (matrix metalloproteinase [MMP]-13 and ADAMTS-4), and structural matrix (COL2A1 [collagen, type II, alpha] and ACAN [aggregan]) genes was higher overall in cartilage from hips with femoroacetabular impingement compared with hips with osteoarthritis and normal controls. The differences reached significance (p ≤ 0.05) for seven of these ten quantified genes, with CXCL3, CXCL6, and COL2A1 being elevated in the femoroacetabular impingement group compared with only the control group and IL-8, CCL3L1, ADAMTS-4, and ACAN being elevated compared with both the osteoarthritis and control groups. When samples were grouped according to the stage of the degenerative cascade, mRNA expression was relatively higher in one of the two middle stages of femoroacetabular impingement (chondromalacia or cleavage/thinning), with the difference reaching significance for IL-8, CXCL2, CXCL3, CCL3L1, and ACAN. ACAN expression was diminished in hips with osteoarthritis compared with femoroacetabular impingement but elevated compared with the control articular cartilage.ConclusionsArticular cartilage from the impingement zone of hips with femoroacetabular impingement (and particularly those hips in the cleavage/thinning stage) expressed higher levels of certain inflammatory, anabolic, and catabolic genes, representing a heightened metabolic state.Clinical relevanceThe articular cartilage from the impingement zone of hips with femoroacetabular impingement was metabolically hyperactive, supporting the concept that such impingement is a structural precursor to hip osteoarthritis.
Project description:Hip dysplasia is known to lead to premature osteoarthritis. Computational models of joint mechanics have documented elevated contact stresses in dysplastic hips, but elevated stress has not been directly associated with regional cartilage degeneration. The purpose of this study was to determine if a relationship exists between elevated contact stress and intra-articular cartilage damage in patients with symptomatic dysplasia and femoroacetabular impingement. Discrete element analysis was used to compute hip contact stresses during the stance phase of walking gait for 15 patients diagnosed with acetabular dysplasia and femoral head-neck offset deformity. Contact stresses were summed over the duration of the walking gait cycle and then scaled by patient age to obtain a measure of chronic cartilage contact stress exposure. Linear regression analysis was used to evaluate the relationship between contact stress exposure and cartilage damage in each of six acetabular subregions that had been evaluated arthroscopically for cartilage damage at the time of surgical intervention. A significant correlation (R2 = 0.423, p < 0.001) was identified between chondromalacia grade and chronic stress-time exposure above both a 1 MPa damage threshold and a 2 MPa-years accumulated damage threshold. Furthermore, an over-exposure threshold of 15% regional contact area exceeding the 1 and 2 MPa-years threshold values resulted in correct identification of cartilage damage in 83.3% (55/66) of the acetabular subregions loaded during gait. These results suggest corrective surgery to alleviate impingement and reduce chronic contact stress exposures below these damage-inducing thresholds could mitigate further cartilage damage in patients with hip dysplasia.
Project description:Femoroacetabular impingement (FAI) has a strong clinical association with the development of hip osteoarthritis (OA); however, the pathobiological mechanisms underlying the transition from focal impingement to global joint degeneration remain poorly understood. The purpose of this study is to use whole-genome RNA sequencing to identify and subsequently validate differentially expressed genes (DEGs) in femoral head articular cartilage samples from patients with FAI and hip OA secondary to FAI. Thirty-seven patients were included in the study with whole-genome RNA sequencing performed on 10 gender-matched patients in the FAI and OA cohorts and the remaining specimens were used for validation analyses. We identified a total of 3531 DEGs between the FAI and OA cohorts with multiple targets for genes implicated in canonical OA pathways. Quantitative reverse transcription-polymerase chain reaction validation confirmed increased expression of FGF18 and WNT16 in the FAI samples, while there was increased expression of MMP13 and ADAMTS4 in the OA samples. Expression levels of FGF18 and WNT16 were also higher in FAI samples with mild cartilage damage compared to FAI samples with severe cartilage damage or OA cartilage. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. We independently validated the results of the sequencing analysis and found increased expression of anabolic markers in patients with FAI and minimal histologic cartilage damage, suggesting that anabolic signaling may be increased in early FAI with a transition to catabolic and inflammatory gene expression as FAI progresses towards more severe hip OA. Clinical significance:Cam-type FAI has a strong clinical association with hip OA; however, the cellular pathophysiology of disease progression remains poorly understood. Several previous studies have demonstrated increased expression of inflammatory markers in FAI cartilage samples, suggesting the involvement of these inflammatory pathways in the disease progression. Our study further expands the knowledge regarding distinct genetic reprogramming in the cartilage between FAI and hip OA patients. In addition to differences in inflammatory gene expression, we also identified differential expression in multiple pathways involved in hip OA progression.
Project description:PurposeWe aimed to determine the relationship between recreational sports and intra-articular hip injuries in an active population that had undergone hip arthroscopy for femoroacetabular impingement syndrome.MethodsA retrospective review was performed of prospectively collected data from patients undergoing hip arthroscopy between January 2015 and December 2016. Inclusion criteria included patients between 18 and 50 years of age who had participated in recreational sports prior to surgery and had a minimum of a 2-year follow-up. Labral injury was evaluated using the Multicenter Arthroscopic Hip Outcome Research Network classification, and rim chondral injuries were evaluated using the Acetabular Labral Articular Disruptions system. Ligamentum teres tear and psoas impingement were also recorded. Sports were classified as rotational running (soccer, basketball, handball), flexibility (martial arts, dance), asymmetric-overhead (racquet), or endurance (running, swimming, cycling). Primary univariate analysis of sports' independent associations, demographic characteristics, intra-articular hip injuries, and outcomes was performed.ResultsPatients included 185 people with a mean age of 36.7 years. Patients participating in rotational running sports and flexibility sports had a significantly greater proportion of rim chondral injuries than those participating in endurance sports or asymmetric overhead sports (P = 0.02). Ligamentum teres tears were significantly associated with flexibility sports (P < 0.001). A total of 84.7%, 67.7%, 67.2%, and 71.2% of patients met minimal clinically important difference levels for the modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS)10 questionnaire with activities of daily living (HOS-ADL), the sports subscale (HOS-SSS), and the International Hip Outcome Tool (iHOT-12), respectively; 94.9%, 66.2% and 62.7% met the patient acceptable symptom state for mHHS, HOS-ADL, and HOS-SSS, respectively; 86.7%, 48.5%, 47.8%, and 32.4% found substantial clinical benefit for mHHS, HOS-ADL, HOS-SSS, and iHOT-12, respectively.ConclusionsRotational running sports were significantly associated with rim chondral injuries. Flexibility sports were significantly associated with rim chondral injuries and ligamentum teres tears. Athletes participating in these sports are more likely to have intra-articular hip injuries than those in the other sports categories.Level of evidenceLevel IV, prognostic case series.
Project description:Purpose of reviewFemoroacetabular impingement is a common cause of hip pain in young patients and has been shown to progress to osteoarthritis. The purpose of this review is to better understand the development of femoroacetabular impingement.Recent findingsRecent literature shows little genetic transmission of FAI. However, molecular studies show strong similarities with the cartilage in osteoarthritis. The development of cam lesions has a strong association with sports participation, particularly at the time of physeal closure suggesting abnormal development. Lumbar, pelvis, and femoral biomechanics may also play an important role in dynamic impingement. In summary, femoroacetabular impingement is a dynamic process with many influences. Further research is needed to clarify the pathophysiology of FAI development in hopes of finding preventative options to reduce symptoms and progression to osteoarthritis.