Cartilage Abnormalities Research Articles

Physeal histological morphology after thermal epiphysiodesis using radiofrequency ablation

BackgroundSeveral treatments have been described for leg length discrepancy. Epiphysiodesis is the most commonly used because of its effectiveness. Thermal epiphysiodesis using radiofrequency ablation (RFA) alters the growth plate morphology without damaging the adjacent articular cartilage; it is a minimally invasive method that has shown excellent results in animal models. This study describes the macro and micro morphology after the procedure.Materials and methodsEpiphysiodesis using RFA was performed in vivo for 8 min (92–98 °C) at two ablation sites (medial and lateral) in one randomly-selected tibia in eight growing pigs. The contralateral tibia was used as control. After 12 weeks, the pigs were killed and the tibiae harvested. The specimens were studied macroscopically and histology samples were obtained. Physeal morphology, thickness and characteristics were then described.ResultsMacroscopically, the articular cartilage was normal in all the treated tibiae. Microscopically, the physis was detected as a discontinuous line on the treated tibiae while it was continuous in all controls. In the control specimens, the mean thickness of the physis was 625 µm (606–639, SD = 14). All the physeal layers were organized. In the ablated specimens, disorganized layers in a heterogeneous line were observed. Bone bridges were identified at the ablation sites. The central part of the physis looked normal. Next to the bone bridge, the physis was thicker and presented fibrosis. The mean thickness was 820 µm (628–949, SD = 130). No abnormalities in the articular cartilage were observed.ConclusionsThermal epiphysiodesis with RFA disrupts the physeal morphology and causes the formation of bone bridges at the ablation sites. This procedure does not damage the adjacent articular cartilage. The damaged tissue, next to the bone bridges, is characterized by disorganization and fibrosis.

Sports Injuries about the Hip: What the Radiologist Should Know.

Injuries of the hip and surrounding structures represent a complex and commonly encountered scenario in athletes, with improper diagnosis serving as a cause of delayed return to play or progression to a more serious injury. As such, radiologists play an essential role in guiding management of athletic injuries. Familiarity with hip anatomy and the advantages and limitations of various imaging modalities is of paramount importance for accurate and timely diagnosis. Magnetic resonance (MR) imaging is often the modality of choice for evaluating many of the injuries discussed, although preliminary evaluation with conventional radiography and use of other imaging modalities such as ultrasonography (US), computed tomography, and bone scintigraphy may be supplementary or preferred in certain situations. Stress fractures, thigh splints, and posterior hip dislocations are important structural injuries to consider in the athlete, initially imaged with radiographs and often best diagnosed with MR imaging. Apophyseal injuries are particularly important to consider in young athletes and may be acute or related to chronic repetitive microtrauma. Femoroacetabular impingement has been implicated in development of labral tears and cartilage abnormalities. Tear of the ligamentum teres is now recognized as a potential cause of hip pain and instability, best evaluated with MR arthrography. Greater trochanteric pain syndrome encompasses a group of conditions leading to lateral hip pain, with US playing an increasingly important role for both evaluation and image-guided treatment. Muscle injuries and athletic pubalgia are common in athletes. Lastly, snapping hip syndrome and Morel-Lavallée lesions are two less common but nonetheless important considerations. ©RSNA, 2016.

Efficacy of intravenous administration of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.

OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups. RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.

Arthroscopy of the Dorsal and Plantar Pouches of the Tarsocrural Joint for the Treatment of Osteochondritis Dissecans in the Horse: Clinical Features and Follow-Up.

To describe the clinical details and pathology within the dorsal and plantar pouches of the tarsocrural joint of a population of horses that underwent arthroscopic surgery for tarsocrural osteochondritis dissecans (OCD). Retrospective cohort study. Horses referred for arthroscopic treatment of tarsocrural OCD between 2005 and 2013 (102 horses; 144 joints). Case records of all horses that had tarsocrural arthroscopy for OCD at Rossdales Equine Hospital, Newmarket, United Kingdom were included. Cases from 3 ECVS Diplomates were included, 1 of whom routinely examined 70 plantar pouches concurrently with routine dorsal pouch investigation. A structured questionnaire was used to obtain follow-up data alongside examination of racing records where appropriate. Descriptive data and 95% CI were calculated. Of the 70 joints that had both dorsal and plantar pouches examined, there was cartilage erosion/degeneration in 22 dorsal pouches (31.4%), cartilage wear lines in 32 plantar pouches (45.7%), and fragments were removed at the time of surgery from 7 plantar pouches (10.0%). Of the plantar pouches with wear lines, 18 (25.7%) had no evidence of cartilage abnormalities (separate from the OCD lesion) within the dorsal pouch. From the 102 horses with available follow-up, 34 horses (66.7%) achieved their intended use postsurgery. Routine plantar pouch investigation is warranted in cases of tarsocrural OCD to provide further information on the health of the joint and allows for removal of fragments from the plantar pouch that may not have been identified by routine diagnostic radiography.

Role of MRI in assessment of patello-femoral derangement in patients with anterior knee pain

ObjectiveTo assess the diagnostic accuracy of magnetic resonance imaging (MRI) in evaluating patello-femoral instability as a cause of anterior knee pain (AKP) and its predisposing factors. Methods55 knees of 50 adult patients below 40 years complaining of AKP underwent MRI between February 2013 and February 2015. The patients were analyzed prospectively for the presence of bone, hyaline cartilage and soft-tissue abnormalities, as well as anatomic variants that may contribute to patello-femoral maltracking or impingement abnormalities. Our results were compared to those of the arthroscopic and mini open exploration procedures. ResultsIn the 55 knees analyzed for patello-femoral instability cartilaginous injuries were found in 58%, with an MRI sensitivity of 88%, disruption of the medial patello-femoral ligament (MPFL) in 31% with an MRI sensitivity 84%, joint morphology abnormalities in 74.5% of patients, bone edema in 27% of patients and Hoffa’s fat pad edema in 30 patients (55%). MRI had a sensitivity of 84% and accuracy of 81% in determining the injury site and pattern. ConclusionMRI is reliable imaging modality in identifying the risk factors that may contribute to the development of patello-femoral maltracking or impingement permitting individual tailored treatment.

Multi-echo GRE imaging of knee cartilage.

To visualize healthy and abnormal articular cartilage, we investigated the potential of using the 3D multi-echo gradient echo (GRE) signal's magnitude and frequency and maps of T2* relaxation. After optimizing imaging parameters in five healthy volunteers, 3D multi-echo GRE magnetic resonance (MR) images were acquired at 3T in four patients with chondral damage prior to their arthroscopic surgery. Average magnitude and frequency information was extracted from the GRE images, and T2* maps were generated. Cartilage abnormalities were confirmed after arthroscopy and were graded using the Outerbridge classification scheme. Regions of interest were identified on average magnitude GRE images and compared to arthroscopy. All four patients presented with regions of Outerbridge Grade I and II cartilage damage on arthroscopy. One patient had Grade III changes. Grade I, II, and III changes were detectable on average magnitude and T2* maps, while Grade II and higher changes were also observable on MR frequency maps. For average magnitude images of healthy volunteers, the signal-to-noise ratio of the magnitude image averaged over three echoes was 4.26 ± 0.32, 12.26 ± 1.09, 14.31 ± 1.93, and 13.36 ± 1.13 in bone, femoral, tibial, and patellar cartilage, respectively. This proof-of-principle study demonstrates the feasibility of using different imaging contrasts from the 3D multi-echo GRE scan to visualize abnormalities of the articular cartilage. © 2016 International Society for Magnetic Resonance in Medicine Level of Evidence: 1 J. MAGN. RESON. IMAGING 2017;45:1502-1513.

Articular cartilage grading of the knee: diagnostic performance of fat-suppressed 3D volume isotropic turbo spin-echo acquisition (VISTA) compared with 3D T1 high-resolution isovolumetric examination (THRIVE).

Background Conventionally, two-dimensional (2D) fast spin-echo (FSE) sequences have been widely used for clinical cartilage imaging as well as gradient (GRE) sequences. Recently, three-dimensional (3D) volumetric magnetic resonance imaging (MRI) has been introduced with one 3D volumetric scan, and this is replacing slice-by-slice 2D MR scans. Purpose To evaluate the image quality and diagnostic performance of two 3D sequences for abnormalities of knee cartilage: fat-suppressed (FS) FSE-based 3D volume isotropic turbo spin-echo acquisition (VISTA) and GRE-based 3D T1 high-resolution isovolumetric examination (THRIVE). Material and Methods The institutional review board approved the protocol of this retrospective review. This study enrolled 40 patients (41 knees) with arthroscopically confirmed abnormalities of cartilage. All patients underwent isovoxel 3D-VISTA and 3D-THRIVE MR sequences on 3T MRI. We assessed the cartilage grade on the two 3D sequences using arthroscopy as a gold standard. Inter-observer agreement for each technique was evaluated with the intraclass correlation coefficient (ICC). Differences in the area under the curve (AUC) were compared between the 3D-THRIVE and 3D-VISTA. Results Although inter-observer agreement for both sequences was excellent, the inter-observer agreement for 3D-VISTA was higher than for 3D-THRIVE for cartilage grading in all regions of the knee. There was no significant difference in the diagnostic performance ( P > 0.05) between the two sequences for detecting cartilage grade. Conclusion FSE-based 3D-VISTA images had good diagnostic performance that was comparable to GRE-based 3D-THRIVE images in the evaluation of knee cartilage, and can be used in routine knee MR protocols for the evaluation of cartilage.

An analysis of changes in in vivo cartilage thickness of the healthy ankle following dynamic activity

Abnormal cartilage loading after injury is believed to be an important factor leading to post-traumatic ankle osteoarthritis. Due to the viscoelastic behavior of cartilage, it is possible to measure localized cartilage strains from changes in thickness following dynamic activities. However, there are limited data characterizing in vivo cartilage mechanics under physiological loading conditions in the healthy ankle. Therefore, the objective of this study was to directly measure in vivo cartilage strains in the healthy ankle joint in response to a dynamic hopping exercise. Ten healthy subjects with no history of ankle injury underwent magnetic resonance imaging before and after a single-leg hopping exercise. Bony and articular cartilage surfaces were created from these images using solid modeling software. Pre-exercise and post-exercise models were then registered to each other, and site-specific cartilage strains (defined as the normalized changes in cartilage thickness) were calculated at grid points spanning the articular surfaces. The effects of both location and exercise on strain were tested using a two-way repeated measures analysis of variance. We did not detect any significant interaction effect between location and exercise for either tibial or talar cartilage. However, hopping resulted in significant decreases in tibial (p<0.05) and talar (p<0.05) cartilage thicknesses, corresponding to strains of 3% and 2%, respectively. Additionally, pre-exercise cartilage thickness varied significantly by location in the talus (p<0.05), but not in the tibia. These strain data may provide important baseline information for future studies investigating altered biomechanics in those at high risk for the development of post-traumatic ankle osteoarthritis.

CORR Insights®: The John Charnley Award: Redefining the Natural History of Osteoarthritis in Patients With Hip Dysplasia and Impingement.

Where Are We Now? Defining the natural history of osteoarthritis remains the “orthopaedic Holy Grail.” Many challenges have kept us from developing a fuller knowledge of the causes of arthritis, including a better understanding of the role of skeletal morphology, the capacity of cartilage to withstand load, the natural process of aging, the impact of disease or genetic factors upon the intrinsic mechanical properties of cartilage, and the cross-talk between cartilage, bone, muscle, nerve and other periarticular tissues. This award-winning paper provides an interesting longitudinal analysis of a cohort of patients with a replaced hip on one side, and a radiographically nonarthritic hip on the other, charting the natural history of the nonoperated hip. Using a longitudinal study design and a carefully selected group of patients, the authors stratified groups by parameters associated with dysplasia and impingement, and found that degenerative changes occurred earliest in patients with dysplasia, while patients with femoroacetabular impingement did not develop arthritis more rapidly than did patients with structurally normal hips. Where Do We Need To Go? The analysis and stratification of specific radiographic parameters is a particularly important part of this analysis, which may allow greater generalizability of the results and application of the analysis in future studies. Still, there are a number of important issues that remain, such as the relative contribution of acetabular and femoral side morphology in the impingement group, the variability of arthritis progression that is present within each grouping of bone morphology, the potential for undefined underlying primary cartilage abnormalities, and the potential confounding factors associated with using a total hip replacement cohort such as gait alternations and other treatment rendered in the course of being a surgical patient. Most importantly for surgeons and their patients, is an understanding of whether surgical treatment will change the natural history. Wyles and colleagues speculate on this issue as it relates to surgery for hip impingement, questioning the role of surgery for impingement patterns when those patients with normal morphology and those with radiographic features of impingement were not found to be different. How Do We Get There? There is a need for additional natural history studies on the relationship between hip morphology and degenerative changes in a nonsurgical cohort that might be more generalizable to the healthy population. For example, the findings of this study could be further developed by a longitudinal population study on patients with healthy hips on both sides identified in an at risk population such as certain groups of athletes, military recruits, or offspring of patients who develop hip joint arthritis. Likewise, the results of this study strongly suggest that investigating radiographic or advanced imaging parameters in greater detail could help define a more patient-specific assessment that correlates with the natural history of arthritis. Finally, more prospective clinical work is needed to define the role of surgical intervention for both dysplasia and impingement, but especially for impingement procedures where there remains a strong surgical and nonsurgical equipoise.

The Effects of Anterior Cruciate Ligament Deficiency on the Meniscus and Articular Cartilage: A Novel Dynamic In Vitro Pilot Study.

Background:Anterior cruciate ligament (ACL) injury increases the risk of meniscus and articular cartilage damage, but the causes are not well understood. Previous in vitro studies were static, required extensive knee dissection, and likely altered meniscal and cartilage contact due to the insertion of pressure sensing devices.Hypothesis:ACL deficiency will lead to increased translation of the lateral meniscus and increased deformation of the medial meniscus as well as alter cartilage contact location, strain, and area.Study Design:Descriptive laboratory study.Methods:With minimally invasive techniques, six 1.0-mm tantalum beads were implanted into the medial and lateral menisci of 6 fresh-frozen cadaveric knees. Dynamic stereo x-rays (DSXs) were obtained during dynamic knee flexion (from 15° to 60°, simulating a standing squat) with a 46-kg load in intact and ACL-deficient states. Knee kinematics, meniscal movement and deformation, and cartilage contact were compared by novel imaging coregistration.Results:During dynamic knee flexion from 15° to 60°, the tibia translated 2.6 mm (P = .05) more anteriorly, with 2.3° more internal rotation (P = .04) with ACL deficiency. The medial and lateral menisci, respectively, translated posteriorly an additional 0.7 mm (P = .05) and 1.0 mm (P = .03). Medial and lateral compartment cartilage contact location moved posteriorly (2.0 mm [P = .05] and 2.0 mm [P = .04], respectively).Conclusion:The lateral meniscus showed greater translation with ACL deficiency compared with the medial meniscus, which may explain the greater incidences of acute lateral meniscus tears and chronic medial meniscus tears. Furthermore, cartilage contact location moved further posteriorly than that of the meniscus in both compartments, possibly imparting more meniscal stresses that may lead to early degeneration. This new, minimally invasive, dynamic in vitro model allows the study of meniscus function and cartilage contact and can be applied to evaluate different pathologies and surgical techniques.Clinical Relevance:This novel model illustrates that ACL injury may lead to significant meniscus and cartilage abnormalities acutely, and these parameters are dynamically measurable while maintaining native anatomy.

Quantitative susceptibility mapping detects abnormalities in cartilage canals in a goat model of preclinical osteochondritis dissecans.

To use quantitative susceptibility mapping (QSM) to investigate changes in cartilage canals in the distal femur of juvenile goats after their surgical transection. Chondronecrosis was surgically induced in the right medial femoral condyles of four 4-day-old goats. Both the operated and control knees were harvested at 2, 3, 5, and 10 weeks after the surgeries. Ex vivo MRI scans were conducted at 9.4 Tesla using TRAFF (relaxation time along a fictitious field)-weighted fast spin echo imaging and QSM to detect areas of chondronecrosis and investigate cartilage canal abnormalities. Histological sections from these same areas stained with hematoxylin and eosin and safranin O were evaluated to assess the affected tissues. Both the histological sections and the TRAFF -weighted images of the femoral condyles demonstrated focal areas of chondronecrosis, evidenced by pyknotic chondrocyte nuclei, loss of matrix staining, and altered MR image contrast. At increasing time points after surgery, progressive changes and eventual disappearance of abnormal cartilage canals were observed in areas of chondronecrosis by using QSM. Abnormal cartilage canals were directly visualized in areas of surgically induced chondronecrosis. Quantitative susceptibility mapping enabled investigation of the vascular changes accompanying chondronecrosis in juvenile goats. Magn Reson Med 77:1276-1283, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

MRI findings associated with development of incident knee pain over 48 months: data from the osteoarthritis initiative

The purpose of this nested case-control study was to identify baseline, incident, and progressive MRI findings visible on standard MRI clinical sequences that were associated with development of incident knee pain in subjects at risk for OA over a period of 48 months. We analyzed 60 case knees developing incident pain (WOMAC(pain) = 0 at baseline and WOMAC(pain) ≥ 5 at 48 months) and 60 control knees (WOMAC(pain) = 0 at baseline and WOMAC(pain) = 0 at 48 months) from the Osteoarthritis Initiative. 3 T knee MRIs were analyzed using a modified WORMS score (cartilage, meniscus, bone marrow) at baseline and after 48 months. Baseline and longitudinal findings were grouped into logistic regression models and compared using likelihood-ratio tests. For each model that was significant, a stepwise elimination was used to isolate significant MRI findings. One baseline MRI finding and three findings that changed from baseline to 48 months were associated with the development of pain: at baseline, the severity of a cartilage lesion in the medial tibia was associated with incident pain--(odds ratio (OR) for incident pain = 3.05; P = 0.030). Longitudinally, an incident effusion (OR = 9.78; P = 0.005), a progressive cartilage lesion of the patella (OR = 4.59; P = 0.009), and an incident medial meniscus tear (OR = 4.91; P = 0.028) were associated with the development of pain. Our results demonstrate that baseline abnormalities of the medial tibia cartilage as well as an incident joint effusion, progressive patella cartilage defects, and an incident medial meniscus tear over 48 months may be associated with incident knee pain. Clinically, this study helps identify MRI findings that are associated with the development of knee pain.

Open reduction and internal fixation for the treatment of fractures of the lateral humeral condyle with an early delayed presentation in children: a radiological and clinical prospective study.

The treatment of late presenting fractures of the lateral humeral condyle in children remains controversial. We report on the outcome for 16 children who presented with a fracture of the lateral humeral epicondyle at a mean of 7.4 weeks (3 to 15.6) after injury and were treated surgically. The mean follow-up was four years (1.1 to 8.9), at which time the mean age of the patients was 8.7 years (3.2 to 17.8). The mean Dhillon functional score improved from 3.3 to 5.6 and the mean overall scores improved from 5.6 to 8.5. A total of seven patients had a fishtail deformity and eight had partial lateral epiphyseal closure. None had avascular necrosis. MRI showed an abnormal cartilage signal, incongruence of the joint surface and partial premature closure of the lateral physis in four patients. Neither age at the time of injury, the time interval between injury and operation, nor the pre-operative function were correlated with the incidence of complications. These results support the use of internal fixation for children with a lateral humeral epicondylar fracture with a delayed presentation. Open reduction and internal fixation yielded a satisfactory outcome within 16 weeks in children with a lateral humeral epicondylar fracture with a delayed presentation.

Signaling Cascades Governing Cdc42-Mediated Chondrogenic Differentiation and Mensenchymal Condensation.

Endochondral ossification consists of successive steps of chondrocyte differentiation, including mesenchymal condensation, differentiation of chondrocytes, and hypertrophy followed by mineralization and ossification. Loss-of-function studies have revealed that abnormal growth plate cartilage of the Cdc42 mutant contributes to the defects in endochondral bone formation. Here, we have investigated the roles of Cdc42 in osteogenesis and signaling cascades governing Cdc42-mediated chondrogenic differentiation. Though deletion of Cdc42 in limb mesenchymal progenitors led to severe defects in endochondral ossification, either ablation of Cdc42 in limb preosteoblasts or knockdown of Cdc42 in vitro had no obvious effects on bone formation and osteoblast differentiation. However, in Cdc42 mutant limb buds, loss of Cdc42 in mesenchymal progenitors led to marked inactivation of p38 and Smad1/5, and in micromass cultures, Cdc42 lay on the upstream of p38 to activate Smad1/5 in bone morphogenetic protein-2-induced mesenchymal condensation. Finally, Cdc42 also lay on the upstream of protein kinase B to transactivate Sox9 and subsequently induced the expression of chondrocyte differential marker in transforming growth factor-β1-induced chondrogenesis. Taken together, by using biochemical and genetic approaches, we have demonstrated that Cdc42 is involved not in osteogenesis but in chondrogenesis in which the BMP2/Cdc42/Pak/p38/Smad signaling module promotes mesenchymal condensation and the TGF-β/Cdc42/Pak/Akt/Sox9 signaling module facilitates chondrogenic differentiation.

Correlation between Focal Nodular Low Signal Changes in Hoffa's Fat Pad Adjacent to Anterior Femoral Cartilage and Focal Cartilage Defect Underlying This Region and Its Possible Implication.

Purpose. This study investigates the association between focal nodular mass with low signal in Hoffa's fat pad adjacent to anterior femoral cartilage of the knee (FNMHF) and focal cartilage abnormality in this region. Method. The magnetic resonance fast imaging employing steady-state acquisition sequence (MR FIESTA) sagittal and axial images of the B1 and C1 region (described later) of 148 patients were independently evaluated by two reviewers and categorized into four categories: normal, FNMHF with underlying focal cartilage abnormality, FNMHF with normal cartilage, and cartilage abnormality with no FNMHF. Results. There was a significant association (p = 0.00) between FNMHF and immediate adjacent focal cartilage abnormality with high interobserver agreement. The absence of focal nodular lesions next to the anterior femoral cartilage has a very high negative predictive value for chondral injury (97.8%). Synovial biopsy of focal nodular lesion done during arthroscopy revealed some fibrocollagenous tissue and no inflammatory cells. Conclusion. We postulate that the FNMHF adjacent to the cartilage defects is a form of normal healing response to the cartilage damage. One patient with FHMHF and underlying cartilage abnormality was rescanned six months later. In this patient, the FNMHF disappeared and normal cartilage was observed in the adjacent region which may support this theory.

Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications.

Osteoarthritis (OA) is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs) in the form of stromal vascular fraction (SVF) may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP), have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA.

Schwartz–jampel syndrome: Clinical and diagnostic phenotype of a rare genetic disorder

The distinctive phenotypic, clinical, skeletal characteristics with the typical electrophysiological features of an 11-year-old male child who presented to the neurology outpatient service are described, with the objective of emphasizing the diagnostic awareness of chondrodystrophic myotonia or Schwartz–Jampel syndrome, a very rare genetic disorder. This autosomal recessive disorder due to mutations in the gene Perlecan leads to abnormal cartilage development and anomalous neuromuscular activity.

Imaging Findings of Pneumothorax Caused by Bronchial Cartilage Hypoplasia in a Dog

A 10-year-old, castrated poodle dog presented with a cough for 2 weeks, and the cough initially developed since very young age. On radiographs, pneumothorax was noticed by characteristics of radiolucent area without pulmonary markings along the thoracic wall and diaphragm, retracted lung lobes from the thoracic wall and severely decreased volume of the left cranial lung lobe with disconnected bronchus. Computed tomography (CT) findings identified several pulmonary air-filled cysts and collapsed lung with abnormal shape and non-tapered end of bronchus, bronchioles at the accessory lobe and left cranial lobe. Also, pneumothorax, pneumomediastinum and subcutaneous emphysema were found. Imaging diagnosis was the spontaneous pneumothorax caused by ruptured emphysematous bullae associated with congenital bronchial cartilage abnormality or bronchial tree malformation. On surgery, hypoplasia of the left cranial lobe, right middle lobe, and accessory lobe with a bulla where air was leaking was identified. The accessory lobe was partially resected and bronchial cartilage hypoplasia was confirmed by histopathologic examination.

Cranial osteological development and abnormalities in northern palm ruff, Seriolella violacea (Guichenot, 1848), larvae and juveniles

Seriolella violacea, a new species to be potentially farmed in Chile and Peru, has shown cranial malformations during farming that could adversely affect its commercial development. This study seeks to generate early knowledge of the osteological development and type of cranial abnormalities that this species presents under culture conditions. Larvae from wild caught broodstock were reared from 1 to 60 days post hatching (DPH) (4.8 ± 0.1 mm TL and 11.8 ± 1.0 mm TL respectively). Larvae samples were collected throughout the experimental trial for recording cranial osteological development and abnormalities in cartilage and bone. At 5.7 ± 0.1 mm TL, coraco-scapular, sclerotic, ethmoid plate and quadrate cartilages were present. At 8.0 ± 0.6 mm TL, early ossification was observed in the jaw, premaxilla and maxilla. At 11.8 ± 1.0 mm TL, the branchiostegal rays, jaw, maxilla and opercular complex were ossified. The first cartilaginous structures observed were the Meckel's cartilage, the branchial arches and the suspensory ligament. The first cranial malformations were detected at 5.7 ± 0.1 mm TL, coinciding with mouth opening. The most frequent malformations were a curvature of the lower jaw (23.1%), abnormal separation between branchial arches and the Meckel's cartilage (19.4%) and bulging jaws (15.7%).

Cathepsin-Mediated Alterations in TGFß-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting.

Hypersecretion of acid hydrolases is a hallmark feature of mucolipidosis II (MLII), a lysosomal storage disease caused by loss of carbohydrate-dependent lysosomal targeting. Inappropriate extracellular action of these hydrolases is proposed to contribute to skeletal pathogenesis, but the mechanisms that connect hydrolase activity to the onset of disease phenotypes remain poorly understood. Here we link extracellular cathepsin K activity to abnormal bone and cartilage development in MLII animals by demonstrating that it disrupts the balance of TGFß-related signaling during chondrogenesis. TGFß-like Smad2,3 signals are elevated and BMP-like Smad1,5,8 signals reduced in both feline and zebrafish MLII chondrocytes and osteoblasts, maintaining these cells in an immature state. Reducing either cathepsin K activity or expression of the transcriptional regulator Sox9a in MLII zebrafish significantly improved phenotypes. We further identify components of the large latent TGFß complex as novel targets of cathepsin K at neutral pH, providing a possible mechanism for enhanced Smad2,3 activation in vivo. These findings highlight the complexity of the skeletal disease associated with MLII and bring new insight to the role of secreted cathepsin proteases in cartilage development and growth factor regulation.