CLINICAL AND IMAGING ASPECTS OF TALAR OSTEOCHONDRITIS: A CASE REPORT FROM GUINEA.

Osteochondral lesions of the dome of the talus are becoming an increasingly frequent problem in sports traumatology, and questioning is a major element in the diagnostic orientation, as these are usually young, athletic patients. The main part of the diagnosis is based on complementary imaging examinations. We report the clinical observation of an adult patient, an athlete, referred to a rheumatology consultation for chronic pain of the right ankle with a mechanical appearance and difficulty in walking. Clinical and paraclinical examinations (standard X-ray, CT scan and magnetic resonance imaging) finally led to the conclusion of an osteochondritis of the talus.

Gouty tophus as a rare cause of a Hepple stage V osteochondral lesion of the talus.

BACKGROUND: Talus osteochondral lesion is commonly associated with trauma, avascular necrosis or even genetic factors, but gouty tophus as a cause of Hepple stage V type talus osteochondral lesion is rare. CASE PRESENTATION: Here, we report a case of an 18-year-old man who complained of left medial deep ankle pain on ambulation. This young man had an extreme liking of sea food rich in purines and also sugar-sweetened drinks. He was diagnosed with a Hepple stage V type talus osteochondral lesion and was treated with medial malleolus osteotomy and an osteochondral graft. The talus osteochondral lesion was found to be a gouty tophus and was completely removed. Hypouricemic therapy was prescribed for 2 months, which allowed the patient to walk with a visual analogue score (VAS) score of 1. He was followed up for 12 months. CONCLUSIONS: Young people with an extreme liking of sea food rich in purines and also sugar-sweetened drinks may be at a risk of developing gout. Acute onset of ankle atraumatic pain, swelling with a high level of serum uric acid and a talus osteochondral lesion with cyst formation should make physicians consider a diagnosis of gout.

Tumor location and type affect local recurrence and joint damage in tenosynovial giant cell tumor: a multi-center study.

Osteochondral destruction and a high recurrence rate after surgery are major concerns that make difficult the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of postoperative local recurrence and osteochondral destruction, as correlated with various demographic factors. Eighty surgically treated patients with intra-articular tumors (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were correlated with local recurrence or development/progression of osteochondral destruction. The 5-year local recurrence free survival rate was 71.4%. Diffuse type (n = 59, localized: n = 21) (P = 0.023) and knee location (P = 0.002) were independent risk factors for local recurrence. Diffuse type (P = 0.009) was a significant risk factor, and knee location (P = 0.001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P = 0.040) and findings of osteochondral destruction at the initial examination (P = 0.029). Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, while local recurrence occurs but osteochondral destruction is less observed in the knee.

Novel polychrome staining distinguishing osteochondral tissue and bone cells in decalcified paraffin sections.

The bone is a dynamic and metabolically active organ in which growth and resorption of the osteochondral matrix is orchestrated by osteoblasts and osteoclasts. For decalcified paraffin-embedded specimens, decalcifying agents alter the staining intensity, and excess decalcification interferes with bone staining. Robust bone staining methods independent of the decalcification conditions and animal species are lacking. In this study, we have developed a novel polychrome staining method, named JFRL staining, which stains the components of osteochondral tissue in different colors. With this staining we could visualize the hyaline cartilage as blue by alcian blue, osteoid as red by picrosirius red, and mineralized bone as green by picro-light green SF or picro-naphthol green B and easily distinguished osteoblasts, osteocytes, and osteoclasts. In mineralized bone, this staining revealed the obvious lamellar structures and woven bone. Notably, this staining was independent of the decalcification conditions and experimental animal species examined. To verify the usefulness of JFRL staining, we observed cotton rat tail which has shorter length and shows a false autotomy. The caudal vertebrae were normally developed via endochondral ossification without a fracture plane. At 6 months of age, the number of chondrocytes declined and the hypertrophic zone was absent at the epiphyseal plate, which might reflect the shorter tail. In conclusion, JFRL staining is the first method to simultaneously distinguish osteochondral matrix and bone cells in one section regardless of decalcifying conditions. This robust staining will provide new information for a wide number of biomedical fields, including bone development, physiology, and pathology.

Operative treatments for osteochondral lesions of the talus in adults: A systematic review and meta-analysis.

PURPOSE: This systematic review aimed to identify the available evidence regarding the comparative effectiveness and safety of various operative treatments in adult patients with osteochondral lesions of the talus (OLT). MATERIALS AND METHODS: The PubMed, Embase, ISI Web of Knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date to September 2019. Two reviewers selected the randomized controlled trials (RCTs) and non-RCTs assessing the comparative effectiveness and safety of various operative treatments for OLT. The meta-analysis was performed using Revman 5.3. RESULTS: Eight studies (1 RCT and 7 non-RCTs) with 375 patients were included in this review. The difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score between the cartilage repair and replacement was not significant. The cartilage regeneration with or without cartilage repair had significant superiority in improving the AOFAS score compared with the cartilage repair. The difference in the magnetic resonance observation of cartilage repair tissue score between the cartilage repair and replacement and between cartilage repair and cartilage repair plus regeneration was significant. CONCLUSIONS: Cartilage regeneration and cartilage repair plus regeneration had significant superiority in improving the ankle function and radiological evaluation of OLT, although the trials included did not have high-level evidence. Moreover, which treatment between the 2 was safer could not be addressed in this review as most of the trials did not report the safety outcome. Further studies are needed to define the best surgical option for treating OLT.

Management of acute lesser toe pain.

Patients with foot pain commonly present to their primary care physicians for their initial management and treatment. These patients and their respective foot or lesser toe pain can present the physician with a complex problem with a long differential list. Depending on the timing of the pain and underlying pathology, these differentials can be divided into acute and acute exacerbation of chronic conditions. This review categorizes the history, physical exam, radiological findings, conservative treatment, and surgical management for each major cause of lesser toe pain, whether acute or chronic. The acute conditions surrounding lesser toe pain in the adult population discussed are toe fractures, toe dislocations, and metatarsal head and neck fractures. The chronic pathologies surrounding lesser toe pain in the adult population evaluated in this review include metatarsalgia, Morton's neuroma, Freiberg infraction, brachymetatarsia, bunionettes, and lesser toe disorders.

Continuous low-intensity ultrasound attenuates IL-6 and TNFα-induced catabolic effects and repairs chondral fissures in bovine osteochondral explants.

BACKGROUND: Cartilage repair outcomes are compromised in a pro-inflammatory environment; therefore, the mitigation of pro-inflammatory responses is beneficial. Treatment with continuous low-intensity ultrasound (cLIUS) at the resonant frequency of 5 MHz is proposed for the repair of chondral fissures under pro-inflammatory conditions. METHODS: Bovine osteochondral explants, concentrically incised to create chondral fissures, were maintained under cLIUS (14 kPa (5 MHz, 2.5 Vpp), 20 min, 4 times/day) for a period of 28 days in the presence or absence of cytokines, interleukin-6 (IL-6) or tumor necrosis factor (TNF)α. Outcome assessments included histological and immunohistochemical staining of the explants; and the expression of catabolic and anabolic genes by qRT-PCR in bovine chondrocytes. Cell migration was assessed by scratch assays, and by visualizing migrating cells into the hydrogel core of cartilage-hydrogel constructs. RESULTS: Both in the presence and absence of cytokines, higher percent apposition along with closure of fissures were noted in cLIUS-stimulated explants as compared to non-cLIUS-stimulated explants on day 14. On day 28, the percent apposition was not significantly different between unstimulated and cLIUS-stimulated explants exposed to cytokines. As compared to non-cLIUS-stimulated controls, on day 28, cLIUS preserved the distribution of proteoglycans and collagen II in explants despite exposure to cytokines. cLIUS enhanced the cell migration irrespective of cytokine treatment. IL-6 or TNFα-induced increases in MMP13 and ADAMTS4 gene expression was rescued by cLIUS stimulation in chondrocytes. Under cLIUS, TNFα-induced increase in NF-κB expression was suppressed, and the expression of collagen II and TIMP1 genes were upregulated. CONCLUSION: cLIUS repaired chondral fissures, and elicited pro-anabolic and anti-catabolic effects, thus demonstrating the potential of cLIUS in improving cartilage repair outcomes.

Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration.

Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.

Healing of Osteochondral Defects via Endochondral Ossification in an Ovine Model.

OBJECTIVE: The objective of this study was to describe the mechanism of healing of osteochondral defects of the distal femur in the sheep, a commonly used translational model. Information on the healing mechanism be useful to inform the design of tissue engineering devices for joint surface defect repair. DESIGN: A retrospective study was conducted examining 7-mm diameter osteochondral defects made in the distal medial femoral condyle of 40 adult female sheep, comprising control animals from 3 separate structures. The healing of the defects was studied at post mortem at up to 26 weeks. RESULTS: Osteochondral defects of the distal femur of the sheep heal through endochondral ossification as evidenced by chondrocyte hypertrophy and type X collagen expression. Neocartilage is first formed adjacent to damaged cartilage and then streams over the damaged underlying bone before filling the defect from the base upward. No intramembranous ossification or isolated mesenchymal stem cell aggregates were detected in the healing tissue. No osseous hypertrophy was detected in the defects. CONCLUSIONS: Osteochondral defects of the medial femoral condyle of the sheep heal via endochondral ossification, with neocartilage first appearing adjacent to damaged cartilage. Unlike the mechanism of healing in fracture repair, neocartilage is eventually formed directly onto damaged bone. There was most variability between animals between 8 and 12 weeks postsurgery. These results should be considered when designing devices to promote defect healing.

Role of Mesenchymal Stem Cells Densities When Injected as Suspension in Joints with Osteochondral Defects.

OBJECTIVE: The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect. DESIGN: At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups ( n = 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs. RESULTS: At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone. CONCLUSION: An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.

A novel method using bone peg fixation for acute osteochondral fracture of the talus: a surgical technique.

INTRODUCTION: The osteochondral fracture of the talus is an uncommon condition, therefore, there are controversies for the optimal treatment. We report a novel surgical technique of bone peg fixation for osteochondral fracture of the talus. MATERIALS AND METHODS: We report two cases that underwent bone peg fixation for the acute osteochondral fractures of talus. Clinical and radiographic evaluations were performed at the last follow-up. RESULTS: At the last follow-up, mean ROM of ankle joint was 50° (range 45°-55°). Additionally, mean VAS and AOFAS score were 0 and 100 at the last follow-up, respectively. All patients obtained bone union without complication at the last follow-up radiographs. CONCLUSIONS: This case study shows good clinical and radiographic results with autologous bone peg fixation in patients with acute osteochondral fractures of the talus. LEVEL OF EVIDENCE: V, expert opinion.

Imaging the Pediatric Athlete: Acute and Stress Skeletal Injuries.

Sports-related traumatic injuries in children have increased in tandem with participation in higher level activities. The developing musculoskeletal structures in children are susceptible to unique injuries that vary with location and the stage of skeletal maturation. The imaging evaluation of sports injuries in children presents several unique challenges. The purpose of this article is to educate the reader on injuries unique to the skeletally immature athlete with focus on their imaging evaluation and diagnosis.

Relation between osteoarthritis and HLA-A in Iraqui patients

Relación entre osteoartritis y HLA - A en pacientes iraquíes. (HLA: acrónimo inglés de antcígenos leucocitarios humanos - Human Leucocyte Antigens). La osteoartritis e la afección más común que involucra el aparato osteo-articular. Representa a un grupo heterogéneo de condiciones resultante de cambios comunes histopatológicos y radiológicos. Existen múltiples factores de riesgo para la osteoartritis: edad, obesidad, y el antígeno genético. El leococitario humano (HLA) como parte del sistema inmune, teniendo un rol en el proceso nosológico. Diversos estudios han determinado la diferente asociación entre la clase HLA - I y la II. El objetivo de esta investigación fue el de determinar la eventualidad de una relación entre el HLA-I y el II en la osteocondritis. Los resultados obtenidos se discuten en el artículo.

Background: Osteoarthritis (OA) is the most common type of joint disease. It represents a heterogeneous group of conditions resulting in common histopathologic and radiologic changes. There are multiples risk factors for osteoarthritis includes the following: Age, Obesity and Genetics. Human leukocyte antigen (HLA) as part of immune system has a role in the disease process. Many reported studies have pointted to different HLA classs I and II association. Aim: To investigate whether there is an association between HLA class II and OA. Patients and methods: A cross sectional comparatives study including patient with primary osteoarthritis attending the department of orthopedic in Al-Kindy teaching hospital Baghdad, Iraq between September 2016-September 2017. Patient's selection was done by the orthopaedics. The HLA-A tuping was performed in HLA research unit at Al-Kindy College of Medicine using PCR-SSO according to the manufacturer instruction using both Amplification and Hybridization kit by Automated method using Autolipa - 48Innogenities-Belgium. The results ewre interepted using LIRAS version 5.0 software innogenetics - Belgium, odds ratio were used to test signifcant differences. Results: Thirty five Iraqi Arab Muslims patients with primary osteoarthritis. The control group was comprised from 75 healtht unrelated sex and age matched volunteers among the staff of Al-Kindey college of medicine that didn't have a history of osteoarthritis. There was an increased frequencies of HLA-A*0101,0202,6802 in patients with osteoarthritis compared with healthy controls (P value=0.001,<0.001,<0.001 respectively)

A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by diffuse testicular microlithiasis and precocious puberty.

BACKGROUND: Bannayan Riley Ruvalcaba syndrome (BRRS) is exceedingly rare, with only about 50 reported cases to date. CASE PRESENTATION: We report a patient with hypoglycemia, precocious puberty and diffuse testicular microlithiasis accompanying BRRS, and think that this case is important in the light of a newly identified mutation in the PTEN gene. CONCLUSIONS: Close attention must be paid in terms of PTEN mutations in cases of macrocephaly and accompanying neurological and dermatological findings.

Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway.

Slow growth and rapid loss of chondrogenic phenotypes are the major problems affecting chronic cartilage lesions. The role of microRNA-195 (miR-195) and its detailed working mechanism in the fore-mentioned process remains unknown. Fibroblastic growth factor 18 (FGF-18) plays a key role in cartilage homeostasis; whether miR-195 could regulate FGF-18 and its downstream signal pathway in chondrocyte proliferation and maintenance of chondrogenic phenotypes still remains unclear. The present research shows elevated miR-195 but depressed FGF-18 expressed in joint fluid specimens of 20 patients with chronic cartilage lesions and in CH1M and CH3M chondrocytes when compared with that in joint fluid specimens without cartilage lesions and in CH1W and CH2W chondrocytes, respectively. The following loss of function test revealed that downregulation of miR-195 by transfection of miR-195 inhibitors promoted chondrocyte proliferation and expression of a type II collagen α I chain (Col2a1)/aggrecan. Through the online informatics analysis we theoretically predicted that miR-195 could bind to a FGF-18 3' untranslated region (3'UTR), also, we verified that a miR-195 could regulate the FGF-18 and its downstream pathway. The constructed dual luciferase assay further confirmed that FGF-18 was a direct target of miR-195. The executed anti-sense experiment displayed that miR-195 could regulate chondrocyte proliferation and Col2a1/aggrecan expression via the FGF-18 pathway. Finally, through an in vivo anterior cruciate ligament transection (ACLT) model, downregulation of miR-195 presented a significantly protective effect on chronic cartilage lesions. Evaluating all of the outcomes of the current research revealed that a decrease of miR-195 protected chronic cartilage lesions by promoting chondrocyte proliferation and maintenance of chondrogenic phenotypes via the targeting of the FGF-18 pathway and that the miR-195/FGF-18 axis could be a potential target in the treatment of cartilage lesions.

Inhibition of the p38-MAPK signaling pathway suppresses the apoptosis and expression of proinflammatory cytokines in human osteoarthritis chondrocytes.

This study aims to investigate the effects of p38-MAPK signaling pathway on the apoptosis and expression of proinflammatory cytokines in human osteoarthritis (OA) chondrocytes. Human articular cartilage specimens were obtained from 57 OA patients and 31 patients with lower extremity traumatic amputations. The expressions of p38-MAPK pathway-related proteins in cartilage tissue were detected by immunochemistry. Cultured chondrocytes isolated from human OA cartilage were assigned into the blank group, the IL-1ß group, the PD (PD980959, ERK pathway inhibitors)+IL-1ß group, the SB (SB203580, p38 pathway inhibitors)+IL-1ß group, and the SP (SP600125, JNK signaling pathway inhibitors)+IL-1ß group. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry. Western blotting was used to detect the expressions of MAPK pathway-related proteins. The mRNA expressions of IL-1, IL-6, and TNF-α were detected by qRT-PCR. The positive rates of p-p38, p-JNK and p-ERK in OA cartilage were higher than those in normal cartilage. Compared with the blank group, cell proliferation rate was decreased, cell apoptotic rate was increased, the mRNA expressions of IL-1, IL-6, TNF-α and the expressions of p-p38, p-JNK and p-ERK were increased in the IL-1ß group, while opposite trends were observed in the PD+IL-1ß, SB+IL-1ß, and SP+IL-1ß groups. Our study provides evidence that inhibition of the p38-MAPK signaling pathway could suppress the apoptosis and expression of proinflammatory cytokines in human OA chondrocytes.

Is there a relationship between talar osteochondral lesions and foot angles?

PURPOSE: We aimed to evaluate the relationship between talar osteochondral defects (OCDs) and foot angles in this study. MATERIALS AND METHODS: We performed a retrospective study that included 25 patients with talar OCD and 29 patients without OCD who underwent magnetic resonance imaging in our department between September 2013 and January 2015. We retrospectively measured the foot angles (Bohler's angle, lateral talocalcaneal angle and calcaneal inclination angle) on ankle radiographs in both groups. RESULTS: Bohler's angle showed no significant differences between the patients (range 20.50°-48.10°, mean 33.40° ± 6.09°) and the control group (range18.80°-42.40°, mean 31.95° ± 4.21°) (p = 0.397). Calcaneal inclination angle showed no significant differences between the patients (range 3°-29.2°, mean 20.55° ± 6.73°) and the control group (range 10.20°-29.80° mean 20.47° ± 4.21°) (p = 0.956). However, talocalcaneal angle was significantly higher in the patients (range 27.80°-44.80°, median 39.50° ± 6.18°) compared with the control group (range 22.60°-40.50°, median 34.10° ± 4.26°) (p = 0.032). CONCLUSION: There is an association between lateral talocalcaneal angle and non-traumatic talar OCD.

Should we use cells, biomaterials, or tissue engineering for cartilage regeneration?

For a long time, cartilage has been a major focus of the whole field of tissue engineering, both because of the constantly growing need for more effective options for joint repair and the expectation that this apparently simple tissue will be easy to engineer. After several decades, cartilage regeneration has proven to be anything but easy. With gratifying progress in our understanding of the factors governing cartilage development and function, and cell therapy being successfully used for several decades, there is still a lot to do. We lack reliable methods to generate durable articular cartilage that would resemble the original tissue lost to injury or disease. The question posed here is whether the answer would come from the methods using cells, biomaterials, or tissue engineering. We present a concise review of some of the most meritorious efforts in each area, and propose that the solution will most likely emerge from the ongoing attempts to recapitulate certain aspects of native cartilage development. While an ideal recipe for cartilage regeneration is yet to be formulated, we believe that it will contain cell, biomaterial, and tissue engineering approaches, blended into an effective method for seamless repair of articular cartilage.