scholarly journals A novel model for the induction of postnatal murine hip deformity

2018 ◽  
Author(s):  
Megan L. Killian ◽  
Penny R. Atkins ◽  
Ryan C. Locke ◽  
Michael G. James ◽  
Andrew E. Anderson ◽  
...  

AbstractAcetabular dysplasia is a recognized cause of hip osteoarthritis (OA). A paucity of animal models exists to investigate structural and functional changes that mediate morphology of the dysplastic hip and drive the subsequent arthritic cascade. Utilizing a novel murine model, this study investigated the role of surgically-induced unilateral instability of the postnatal hip on the initiation and progression of acetabular dysplasia and impingement up to 8-weeks post-injury. Specifically, C57BL6 mice were used to develop titrated levels of hip instability (mild, moderate, severe, and femoral head removal) at 3-weeks of age, a critical time for hip maturation. Joint shape, acetabular coverage, histomorphology, immunohistochemistry, and statistical shape modeling were used to assess overall quality of joint health and three-dimensional hip shape following 8 weeks of titrated destabilization. This titrated approach included mild, moderate, severe, and complete instability via surgical destabilization of the murine hip. Acetabular coverage was reduced following severe, but not moderate, instability. Moderate instability induced lateralization of the femoral head without dislocation, whereas severe instability led to complete dislocation and formation of pseudoacetabula. Mild instability did not result in statistically significant morphological changes to the hip. Complete destabilization via femoral head removal led to reduced joint space volume and reduced bone volume ratio in the remnant proximal femur. Collectively, these results support the notion that hip instability, driven by loss of function, leads to morphometric changes in the maturing mouse hip. This model could be useful for future studies investigating the mechanical and cellular adaptations to hip instability during maturation.

2018 ◽  
Vol 26 (2) ◽  
pp. 230949901876803 ◽  
Author(s):  
Oktay Adanir ◽  
Gazi Zorer

Introduction: Hip osteoarthritis is an important orthopedic problem frequently observed in the elderly. Acetabular dysplasia (AD) is one of the pathologies that cause coxarthrosis. Nearly 20–45% of primary or idiopathic hip osteoarthritis is linked to AD. In our country, there are few studies on this topic. We measured the center–edge (CE) angle, Sharp’s angle, acetabular depth, and femoral head coverage ratio on pelvis anteroposterior radiographs of patients with primary coxarthrosis and calculated the dysplasia rates. Patients and method: Age at surgery and sex of the patients; and CE angle, Sharp’s angle, acetabular depth, and femoral head coverage ratio for both operated and opposite hips were evaluated in 223 total hip prosthesis–performed patients with coxarthrosis. Also the distribution of mean age at surgery, sex of patients, dysplasia rates of operated hips, and bilateral dysplasia rates were calculated. Results: The right to left ratio of operated hips was 104/119. Female to male ratio was 163/60 (2.7/1), for those with CE angle below 20° it was 123/30 (4.1/1), and it was 40/30 (1.3/1) with CE angle above 20°. Mean age of patients at surgery was 56.9 (±11.4) years. CE angle less than 20° was found in 68.6% of patients, acetabulum depth less than 9 mm was found in 75.3%, Sharp’s angle was more than 45° in 65.9%, and femoral head coverage ratio was less than 70% in 70.3% of patients. Conclusions: We identified a high rate of AD in primary coxarthrosis patients undergoing total hip arthroplasty in the study population.


2020 ◽  
Vol 28 (3) ◽  
pp. 230949902095710
Author(s):  
Arif Jan Hamrayev ◽  
Mehmet Ozbey Buyukkuscu ◽  
Abdulhamit Misir ◽  
Sukru Sarper Gursu

Purpose: To evaluate the acetabular cup and graft survival in patients who underwent total hip arthroplasty (THA) with the diagnosis of dysplastic hip osteoarthritis and received a femoral head autograft due to acetabular coverage deficiency. Methods: Between January 2005 and December 2016, 83 hip prostheses of 80 patients who underwent THA using femoral head autografts and were followed up for at least 2 years were retrospectively evaluated. Seventy-four hips of the remaining 71 patients (57 female (80%)) were included. Mean patient age at surgery was 51 ± 16 (range 18–76) years. The mean follow-up duration was 76 ± 25 (range 25–161) months. Acetabular inclination and graft thickness, contact length, percentage of coverage, and graft resorption were examined on postoperative and final follow-up radiographs. The presence of a radiolucent area around the acetabular and femoral components indicating loosening was also evaluated. Results: The mean postoperative acetabular component inclination was 44 ± 5.1° (range 30–48°) with mean graft coverage of 34 ± 4.8% (range 24–46%). In all patients, autograft union with the pelvis was seen and the lateral overflow was remodeled. Fifteen patients (20%) underwent revision surgery due to aseptic acetabular component loosening in four, nontraumatic recurrent dislocations in eight, periprosthetic infection in one, acetabular component protrusion in one, and traumatic hip dislocation in one. Conclusion: In patients with osteoarthritis secondary to developmental hip dysplasia, the use of femoral head autografts to eliminate acetabular coverage deficiency during THA achieves acceptable midterm postoperative radiological outcomes. Increased acetabular bone stock may be beneficial in possible future revision surgeries.


2020 ◽  
Vol 8 (4_suppl3) ◽  
pp. 2325967120S0020
Author(s):  
Elizabeth Graesser ◽  
Maria Schwabe ◽  
Sean Akers ◽  
Cecilia Pascual-Garrido ◽  
John C Clohisy ◽  
...  

Introduction: Assessment of anterior acetabular coverage is commonly done with measurement of the anterior center edge angle (ACEA) or anterior wall index (AWI). This is particularly important in cases of borderline acetabular dysplasia where it may influence treatment decisions. However, the ACEA and AWI has been poorly validated. Purpose: The purpose of the current study was to investigate the correlation between plain radiographic measurements and three-dimensional femoral head coverage on low-dose CT in borderline acetabular dysplasia. Methods: Seventy consecutive hips with borderline acetabular dysplasia (LCEA 20-25°) were included in the current study. Radiographic evaluation was performed prospectively including LCEA, acetabular inclination, and AWI on AP pelvis radiographs, and ACEA on false profile radiographs. The mean LCEA was 22.1±1.4°, while the mean acetabular inclination was 10.3±3.3. All patients underwent low-dose pelvic CT assessment for preoperative planning. The radial acetabular coverage was calculated according to the standardized clock-face position [measured at 12:00 (lateral), 1:00, 2:00, 3:00 (anterior), and 4:00] as described by Larson et al. Statistical analysis determined the correlation between ACEA and radial coverage. Results: The mean ACEA in the group was 25.3±5.8° (range 10.1-43.9), with 16% having ACEA≤20° and 50% having ACEA≤25°. The mean radial coverages were 63.5%±1.7 (12:00), 60.7%±2.2 (1:00), 50.8%±3.2 (2:00), 37.0%±3.3 (3:00), and 27.9%±3.1 (4:00). The ACEA had poor correlation with radial coverage at all positions from 12:00 to 4:00 (range –0.068-0.173). The AWI had moderate correlation with radial coverage at 3:00 (PCC 0.499) and 4:00 (PCC 0.573). Comparing hips with an ACEA <20° versus >20°, there was no difference between the mean radial acetabular coverage at any position 12:00-4:00 (p=0.18-0.95). Comparing hips with an ACEA <25° versus >25°, there was no difference between the mean radial acetabular coverage at any position 12:00-4:00 (p=0.12-0.71). No significant difference in AWI was present between subgroups with normal and deficient radial coverage from 12:00 to 4:00 (p=0.09-0.72). Discussion: The current study demonstrates poor correlation of the ACEA measurement with true anterior femoral head coverage as evaluated at clock-face positions from 12:00 to 4:00. The AWI demonstrated moderate correlation for 3:00-4:00 coverage but fails to differentiate hips with normal and deficient coverage. In the setting of borderline acetabular dysplasia, anterior and anterolateral femoral coverage should be assessed via low-dose CT rather than ACEA or AWI.


Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.


2021 ◽  
pp. 1-12
Author(s):  
Meng Wu ◽  
Ming Li ◽  
Hong-Ju Xie ◽  
Hong-Wei Liu

Silicone implant-based augmentation rhinoplasty or mammoplasty induces capsular contracture, which has been acknowledged as a process that develops an abnormal fibrotic capsule associated with the immune response to allogeneic materials. However, the signaling pathways leading to the nasal fibrosis remain poorly investigated. We aimed to explore the molecular mechanism underlying the pathogenesis of nasal capsular contracture, with a specific research interest in the signaling pathways involved in fibrotic development at the advanced stage of contracture. By examining our recently obtained RNA sequencing data and global gene expression profiling between grade II and grade IV nasal capsular tissues, we found that both the RAP1 and JAK/STAT signaling pathways were hyperactive in the contracted capsules. This was verified on quantitative real-time PCR which demonstrated upregulation of most of the representative component signatures in these pathways. Loss-of-function assays through siRNA-mediated Rap1 silencing and/or small molecule-directed inhibition of JAK/STAT pathway in ex vivo primary nasal fibroblasts caused a series of dramatic behavioral and functional changes, including decreased cell viability, increased apoptosis, reduced secretion of proinflammatory cytokines, and synthesis of type I collagen, compared to control cells, and indicating the essential role of the RAP1 and JAK/STAT signaling pathways in nasal capsular fibrosis. Our results sheds light on targeting downstream signaling pathways for the prevention and therapy of silicone implant-induced nasal capsular contracture.


2021 ◽  
pp. 112070002110130
Author(s):  
Leigh-Anne Tu ◽  
Douglas S Weinberg ◽  
Raymond W Liu

Background: While the influences of acetabular dysplasia and overcoverage on hip arthritis have been studied, the impact of femoral neck-shaft angle on hip arthritis is much more poorly understood. The purpose of this study is to determine if a relationship exists between neck shaft angle and the development of osteoarthritis, a better understanding of which would be useful to surgeons planning osteotomies about the hip. Methods: 533 cadaveric femora and acetabulae (1066 total) from the Hamann-Todd Osteological Collection (Cleveland, OH) were acquired. We measured true neck shaft angle using an AP photograph with the femoral neck parallel to the table. Femoral head volume to acetabular volume ratio, representing femoral head coverage, as well as femoral version were utilised. Correlation between neck shaft angle, femoral version, femoral head coverage and osteoarthritis were evaluated with multiple regression analysis. Results: The mean age and standard deviation was 56 ± 10 years. There were 64 females (12%) and 469 males. There were 380 Caucasians (71%) and 153 African-Americans. Mean femoral version was 11° ± 12° and mean true neck shaft angle was 127.7° ± 5.9° There was a strong correlation between age and arthritis (standardised beta 0.488, p < 0.001). There was a significant correlation between increasing true neck shaft angle and decreasing hip arthritis (standardised beta -0.024, p = 0.038). In the femoral head overcoverage subset, increasing true neck shaft angle was still significantly associated with decreasing hip arthritis (standardised beta −0.088, p = 0.018), although this relationship was not significant with femoral head undercoverage subset. Conclusions: With sufficient acetabular coverage, a relative increase in femoral neck shaft angle within the physiologic range is associated with decreased hip osteoarthritis. Clinical relevance: An understanding of the relationship between femoral neck shaft angle and hip osteoarthritis could be useful for surgeons planning pelvic or proximal femur osteotomies in children.


2021 ◽  
Vol 9 (7_suppl3) ◽  
pp. 2325967121S0016
Author(s):  
Elizabeth Graesser ◽  
Maria Schwabe ◽  
Cecilia Pascual Garrido ◽  
John C. Clohisy ◽  
Jeffrey J. Nepple

Introduction: Borderline acetabular dysplasia is classically defined as a lateral center edge angle (LCEA) of 20-25 degrees. The optimal treatment strategy in this patient group remains controversial, with some patients having primarily hip instability-based symptoms, while others have primarily impingement-based symptoms (non-instability). The purpose of the current study was to define the 3D characteristics on low-dose CT that differentiate patients with instability symptoms from those without instability in the setting of borderline acetabular dysplasia. Methods: Seventy consecutive hips with borderline acetabular dysplasia undergoing surgical treatment were included in the current study. All patients underwent low-dose pelvic CT with femoral version assessment for preoperative planning. CT measurements included alpha angle and radial acetabular coverage (RAC) at standardized clockface positions (9:00-posterior to 3:00-anterior), central and cranial acetabular version. RAC was assessed in three sectors (anterior, superior, and posterior) and defined (relative to published normative data) as normal (-1 SD, +1 SD), undercoverage (<-1 SD), or overcoverage (>+1 SD). Statistical analysis was performed to compare the CT characteristics of the symptomatic instability and non-instability groups. Results: Of the 70 hips, 62.9% had the diagnosis of symptomatic instability, while 37.1% had no instability symptoms. Hips with instability (compared to non-instability) had significantly lower alpha angle (maximal difference at 1:00 - 47.0° vs. 59.4°), increased femoral version (22.3° vs. 15.3°), and decreased radial acetabular coverage (maximal difference at 1:00 – 59.9% vs. 62.2%) (all p<0.001). Multivariate analysis identified femoral version (OR 1.1, p=0.02), alpha angle at 1:00 (OR 0.91, p=0.02), and RAC at 1:00 (OR 0.46, p=0.003) as independent predictors of the presence of instability. The model combining these three factors had excellent predictive probability with a c-statistic 0.92. Conclusion: We found significant differences in the 3D hip morphology of the symptomatic instability and non-instability subgroups within the borderline dysplasia cohort. In the setting of borderline dysplasia, three-dimensional deformity characterization with low-dose CT allowed for differentiation of patients diagnosed with underlying instability vs. non-instability. Femoral version, alpha angle at 1:00, and radial acetabular coverage at 1:00 were identified as independent predictors of diagnosis in borderline acetabular dysplasia. Summary: This study attempts to define 3D CT characteristics to help distinguish between patients with impingement-based vs instability-based symptoms of borderline acetabular dysplasia.


2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Keiichiro Akeo ◽  
Shuhei Kameya ◽  
Kiyoko Gocho ◽  
Daiki Kubota ◽  
Kunihiko Yamaki ◽  
...  

Purpose. To report the morphological and functional changes associated with a regression of foveoschisis in a patient with X-linked retinoschisis (XLRS).Methods. A 42-year-old man with XLRS underwent genetic analysis and detailed ophthalmic examinations. Functional assessments included best-corrected visual acuity (BCVA), full-field electroretinograms (ERGs), and multifocal ERGs (mfERGs). Morphological assessments included fundus photography, spectral-domain optical coherence tomography (SD-OCT), and adaptive optics (AO) fundus imaging. After the baseline clinical data were obtained, topical dorzolamide was applied to the patient. The patient was followed for 24 months.Results. A reportedRS1gene mutation was found (P203L) in the patient. At the baseline, his decimal BCVA was 0.15 in the right and 0.3 in the left eye. Fundus photographs showed bilateral spoke wheel-appearing maculopathy. SD-OCT confirmed the foveoschisis in the left eye. The AO images of the left eye showed spoke wheel retinal folds, and the folds were thinner than those in fundus photographs. During the follow-up period, the foveal thickness in the SD-OCT images and the number of retinal folds in the AO images were reduced.Conclusions. We have presented the detailed morphological changes of foveoschisis in a patient with XLRS detected by SD-OCT and AO fundus camera. However, the findings do not indicate whether the changes were influenced by topical dorzolamide or the natural history.


Development ◽  
1993 ◽  
Vol 119 (3) ◽  
pp. 711-720 ◽  
Author(s):  
U. W. Rothenpieler ◽  
G. R. Dressler

The conversion of mesenchyme to epithelium during the embryonic development of the mammalian kidney requires reciprocal inductive interactions between the ureter and the responding metanephric mesenchyme. The Pax-2 gene is activated in the mesenchyme in response to induction and is subsequently down-regulated in more differentiated cells derived from the mesenchyme. Pax-2 belongs to a family of genes, at least three of which encode morphogenetic regulatory transcription factors. In order to determine the role of Pax-2 during kidney development, we have generated a loss- of-function phenotype using antisense oligonucleotides in mouse kidney organ cultures. These oligonucleotides can specifically inhibit Pax-2 protein accumulation in kidney mesenchyme cells, where the intracellular concentrations are maximal. The kidney organ cultures were stained with uvomurulin and laminin antibodies as markers for epithelium formation. With significantly reduced Pax-2 protein levels, kidney mesenchyme cells fail to aggregate and do not undergo the sequential morphological changes characteristic of epithelial cell formation. The data demonstrate that Pax-2 function is required for the earliest phase of mesenchyme-to-epithelium conversion.


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