Ossification Of Cartilage Research Articles

Age estimation from endochondral ossification pattern of thyroid cartilage in the population of Punjab

Objective: The present study aims at studying the ossification of thyroid cartilage and to compare it with age of the individual. Methods: The study was conducted in 300 samples of thyroid cartilage collected during autopsy in the department of Forensic medicine in a tertiary care hospital. Each thyroid cartilage is divided in to thirteen anatomical area and ossification in each defined area was studied through gross and cut section features and classified as ossified and not ossified areas. The samples were grouped in to seven groups of age and ossification features were compared between the age groups. Results: On analysing the ossification pattern of thyroid cartilage in thirteen defined anatomical areas and comparing it with the age, a peculiar sequence of ossification was noted, and it was also observed that frequency of ossification increases significantly with increasing age groups. Conclusion: Ossification of thyroid cartilage helps in establishing the age of individual and it can be categorised to an age group of ten years.

Delayed Correction of Intra-articular Lateral Head Fracture of the Proximal Phalanx of the Great Toe in Children.

Conservative treatment of intra-articular lateral head fracture of the proximal phalanx (LHFPP) of the great toe in young children has a high rate of nonunion, leading to hallux valgus interphalangeus (HVIP). This study presents a case series of surgically managed, late-diagnosed LHFPP, highlighting the difficulties of the surgery and presenting satisfactory results. Nine unilateral cases (8 late-diagnosed and 1 acute) were treated by open reduction and Kirchner wire fixation. The average time from trauma to surgery was 2.9 years (range, 0.5-10.1 years) in our late-diagnosed cases. The average age at the time of operation was 9.2 years (range, 3.4-16.3 years). The causes of injury were various. Intraoperative findings were reviewed through medical records and photographs. Pre- and postoperative HVIP angle, American Orthopedic Foot and Ankle Society (AOFAS) score, and range of motion of the interphalangeal joint were measured and compared statistically. Progressive HVIP was a chief complaint in all 8 late-diagnosed cases. Bony fragment size depended on the time elapsed after trauma (fragments increased in size due to ossification of cartilage) with a mean of 23.5% articular involvement. Four cases required bone graft, and union was achieved in all cases. The mean HVIP angle improved from a mean of 17.8° to 10.5°. The average AOFAS score and range of motion were significantly improved after surgery. Although LHFPP is rare and difficult to diagnose, even cases detected long after the initial trauma can be successfully treated, albeit with difficulty. All 9 of our patients had successful outcomes when treated by open reduction and internal fixation.

Comparison of distal extremity magnetic resonance imaging findings in Australian racing Standardbreds and Thoroughbreds.

Foot-related lameness is common in Standardbred and Thoroughbred racehorses. Magnetic resonance imaging (MRI) provides information on both the soft tissue and osseous structures of the distal extremity. The aim of this study was to determine whether abnormalities identified on distal limb MRI differed between these two racehorse populations. The records of Standardbred and Thoroughbred racehorse distal extremity MRI examinations conducted at Camden Equine Centre and Ballarat Veterinary Practice between 2013 and 2023 were retrieved. Horses were included if pain causing lameness had been localised to the foot using perineural or intra-articular analgesia. MRI abnormalities of the structures within the distal extremity were recorded and comparisons made between the two groups. There was a significant difference in the rate of occurrence of certain MRI abnormalities between the Thoroughbred and Standardbred racehorse populations, including distal phalangeal fractures, proximal phalangeal short tau inversion recovery (STIR) hyperintensity (distal aspect), the presence and severity of ungular cartilage ossification, abnormalities of the navicular bone distal border synovial invaginations/vascular channels and navicular bone distal border fragments. The presence of distal extremity STIR hyperintensity and fractures was significantly higher in Standardbred compared to Thoroughbred racehorses when these findings were grouped and considered in combination. There were many similarities in the distal extremity MRI abnormalities identified in lame Australian Standardbred and Thoroughbred racehorses. However, distal phalangeal fractures, ungular cartilage ossification and distal extremity STIR hyperintensity were identified in significantly more in Standardbred than Thoroughbred racehorses.

Utility of the morphological scoring of costal cartilage ossification in age estimation of adult Egyptians using multidetector computed tomography

Abstract Age estimation of adults is a challenging procedure in forensic practice. Inspired by the previous work by Chinese scholars, we established population specific age estimation models from the osseous and calcified projections (OCP) of costal cartilages, using three-dimensional volume-rendering technique. A total of 168 clinical CT scans (2 mm slice thickness) were used to develop the sex-specific age prediction models from a sample of Egyptians, comprising 70 females and 98 males, with documented ages between 12 and 85 years. The sample was also used for validating the Chinese model. We reported the differences between the predictive accuracy of the Egyptian (population specific) and Chinese (non population specific) models. The most accurate age estimation model was stepwise linear regression with standard error of estimates (SEE) of 10.9 and 11.8 years in males and females, respectively. For the simple linear regression models, the most accurate formula included OCP of the right second costal cartilage in males and OCP of the left third costal cartilage in females with SEE of 11.2 and 12.2 years, respectively and mean absolute error (MAE) of 8.8 and 9.6 years, respectively. By comparison, the best accuracy rates produced by the Chinese vs. the Egyptian models in males and females within 5 years were 30.61% and 32.86% vs. 35.71% and 32.86%, respectively, whereas within 10 years, the accuracy rates increased up to 57.14% and 58.57% vs. 72.45% and 64.29%, respectively. Although the accuracy rates from the Chinese models were lower than those obtained from the Egyptian models, the MAE and least error values were comparable in both sexes. Notable accurate age estimation rates in the advanced age group ≥40 years were reached being 81.25% to 97.92% in males and 69.77% to 93.02% in females. OCP of the right first costal cartilage was the most accurate in cross-population application for males and females with MAE values of 10.7 and 11.03 years, respectively with balanced accuracy rates of age estimation using the 10-year interval and 40-year cutoff.

Endocrine Petrified Ear: Associated Endocrine Conditions in Auricular Calcification/Ossification (A Sample-Focused Analysis).

Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was to highlight most recent PE data and associated endocrine (versus non-endocrine) ailments in terms of presentation, imagery tools, hormonal assessments, biopsy, outcome, pathogenic features. This was a comprehensive review via PubMed search (January 2000-March 2024). A total of 75 PE subjects included: 46 case reports/series (N = 49) and two imagery-based retrospective studies (N = 26) with CAC/OAC prevalence of 7-23% (N = 251) amid routine head/temporal bone CT scans. Endocrine PE (EPE): N = 23, male/female ratio = 10.5; average age = 56.78, ranges: 22-79; non-EPE cohort: N = 26; male/female ratio = 1.88, mean age = 49.44; ranges: 18-75 (+a single pediatric case).The longest post-diagnosis follow-up was of 6-7 years. The diagnosis of PE and endocrine anomalies was synchronous or not (time gap of 10-20 years). A novel case in point (calcified EPE amid autoimmune poly-endocrine syndrome type 2 with a 10-year post-diagnosis documented follow-up) was introduced. We re-analyzed EPE and re-classified another five subjects as such. Hence, the final EPE cohort (N = 50) showed: adrenal insufficiency was the most frequent endocrine condition (36%) followed by hypopituitarism (22%) and hypothyroidism (18%); 39% of the patients with adrenal failure had Addison's disease; primary type represented 72% of all cases with hypothyroidism; an endocrine autoimmune (any type) component was diagnosed in 18%. We propose the term of "endocrine petrified ear" and a workflow algorithm to assess the potential hormonal/metabolic background in PE.

Investigation of the Position and Angle of the Vocal Fold Projected onto the Thyroid Cartilage.

To perform laryngeal framework surgery for unilateral vocal fold paralysis and obtain favorable voice improvement, it is necessary to accurately determine the vocal fold and arytenoid cartilage positions. Thus, the position and angle of the paralyzed vocal folds and arytenoid cartilage projected onto the affected thyroid plate were measured using computed tomography (CT) before and after surgery. Forty-six male patients with thyroid cartilage ossification observed on preoperative CT and vocal fold paralysis were included. Using Adobe Illustrator®, the thyroid plate on the affected side was reconstructed from the continuous images of the sagittal section of the CT examination during participant's quiet breathing (reconstructed affected thyroid plate [RATP]). The anterior commissure mean position was slightly cranial to the midpoint of the thyroid cartilage midline. The paralyzed vocal fold angle was not parallel to the baseline. The average unaffected vocal fold angle during vocalization projected onto the affected thyroid plate was 13.83°, which differed significantly from the average paralyzed vocal fold angle before surgery (19.05°). However, no significant difference was observed in comparison with the average angle of the paralyzed vocal fold after arytenoid adduction. The average distance from the inferior notch of the affected side thyroid cartilage to the affected arytenoid cartilage was 16.7 mm. By understanding the positional relationship between the thyroid cartilage plate and internal structure from preoperative CT images, more effective surgery can be performed according to individual differences. IV Laryngoscope, 134:4088-4094, 2024.

New advances in the treatment of chondrosarcoma under the PD-1/PD-L1 pathway.

Bone sarcomas encompass a group of spontaneous mesenchymal malignancies, among which osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma are the most common subtypes. Chondrosarcoma, a relatively prevalent malignant bone tumor that originates from chondrocytes, is characterized by endogenous cartilage ossification within the tumor tissue. Despite the use of aggressive treatment approaches involving extensive surgical resection, chemotherapy, and radiotherapy for patients with osteosarcoma, chondrosarcoma, and chordoma, limited improvements in patient outcomes have been observed. Furthermore, resistance to chemotherapy and radiation therapy has been observed in chondrosarcoma and chordoma cases. Consequently, novel therapeutic approaches for bone sarcomas, including chondrosarcoma, need to be uncovered. Recently, the emergence of immunotherapy and immune checkpoint inhibitors has garnered attention given their clinical success in various diverse types of cancer, thereby prompting investigations into their potential for managing chondrosarcoma. Considering that circumvention of immune surveillance is considered a key factor in the malignant progression of tumors and that immune checkpoints play an important role in modulating antitumor immune effects, blockers or inhibitors targeting these immune checkpoints have become effective therapeutic tools for patients with tumors. One such checkpoint receptor implicated in this process is programmed cell death protein-1 (PD-1). The association between PD-1 and programmed cell death ligand-1 (PD-L1) and cancer progression in humans has been extensively studied, highlighting their remarkable potential as biomarkers for cancer treatment. This review comprehensively examines available studies on current chondrosarcoma treatments and advancements in anti-PD-1/PD-L1 blockade therapy for chondrosarcoma.

Review of Thyroid Cartilage Compression of the Vertebral Artery

Thyroid cartilage compression of the Vertebral Artery (VA) has been implicated as a rare cause of Rotational Vertebral Artery Occlusion (RVAO). 10 cases have been reported in the literature. This has a higher tendency to affect males and younger patients than other forms of stroke. Patients present with multiple episodes prior to diagnosis. Radiologic studies prove crucial for confirming this condition. An aberrant VA course appears to be a necessary factor. All cases suffer from right side VA compression by the superior thyroid cornu. Conservative therapy with antiplatelet treatment is employed commonly. Most patients have definitive treatment with surgical resection of the right superior thyroid cornu. Theories proposed for these characteristics include VA dominance, structural variability in the thyroid cartilage between genders and also variable thyroid cartilage ossification. Given these findings, we propose the term “thyro-vertebral artery syndrome” for this condition.

IL-6 Reduces Spheroid Sizes of Osteophytic Cells Derived from Osteoarthritis Knee Joint via Induction of Apoptosis

Osteophytes in osteoarthritis (OA) joints contribute to restriction of joint movement, joint pain, and OA progression, but little is known about osteophyte regulators. Examination of gene expression related to cartilage extracellular matrix, endochondral ossification, and growth factor signaling in articular cartilage and osteophytes obtained from OA knee joints showed that several genes such as COL1A1, VCAN, BGLAP, BMP8B, RUNX2, and SOST were overexpressed in osteophytes compared with articular cartilage. Ratios of mesenchymal stem/progenitor cells, which were characterized by co-expression of CD105 and CD166, were significantly higher in osteophytic cells than articular cells. A three-dimensional culture method for cartilage and osteophyte cells was developed by modification of cultures of self-assembled spheroid cell organoids (spheroids). These spheroids cultured in the media for mesenchymal stem cells containing transforming growth factor-β3 showed characteristic morphologies and gene expression profiles of articular cartilage and osteophytes, respectively. The effects of IL-1β, tumor necrosis factor-α, and IL-6 on the spheroids of articular and osteophytic cells were studied. To the best of our knowledge, they provide the first evidence that IL-6 suppresses the spheroid size of osteophytic cells by inducing apoptosis and reducing extracellular matrix molecules. These data show that IL-6 is the suppressor of osteophyte growth and suggest that IL-6 expression and/or activity are implicated in the regulation of osteophyte formation in pathologic joints.

Single-cell RNA sequencing reveals neurovascular-osteochondral network crosstalk during temporomandibular joint osteoarthritis: Pilot study in a human condylar cartilage

PurposeTemporomandibular joint osteoarthritis (TMJ-OA) is one of the most complex temporomandibular disorders, causing pain and dysfunction. The main pathological feature of TMJ-OA is neurovascular invasion from the subchondral bone to the condylar cartilage. This study aimed to discover the cells and genes that play an important role in the neurovascular–osteochondral network crosstalk in human TMJ-OA. Materials and methodsCondylar cartilages from patient with TMJ-OA were divided into OA group, and others from patients with benign condylar hyperplasia (CH) were used as control for further single-cell RNA-sequencing (scRNA-seq). Hematoxylin and eosin staining were performed. The cells and genes in the condylar cartilage were identified and analyzed by scRNA-seq. ResultsHistological analysis revealed blood vessel invasion and ossification in the TMJ-OA condylar cartilage. The scRNA-seq identified immune cells, endothelial cells, and chondrocytes in the TMJ-OA condylar cartilage. Macrophages, especially M1-like macrophages, contributed to the inflammation, angiogenesis, and innervation. CD31+ endothelial cells contributed to the bone mineralization. The TMJ-OA cartilage chondrocytes highly expressed genes related to inflammation, angiogenesis, innervation, and ossification. The hub genes contributing to these processes in the TMJ-OA chondrocytes included CTGF, FBN1, FN1, EGFR, and ITGA5. ConclusionOur study marks the first time scRNA-seq was used to identify the cells and genes in a human TMJ-OA condylar cartilage, and neurovascular–osteochondral network crosstalk during the human TMJ-OA process was demonstrated. Targeting the crosstalk of these processes may be a potential comprehensive and effective therapeutic strategy for human TMJ-OA.

MiR-335-5p inhibits endochondral ossification by directly targeting SP1 in TMJ OA.

During the development of temporomandibular joint osteoarthritis, endochondral ossification is compromised which leads to condylar degeneration; miR-335-5p in endochondral ossification in osteoarthritic condylar cartilage tissue remains unclear. Up-regulated microRNA and its target gene were searched for endochondral ossification in osteoarthritis articular cartilage. The effect of increased or decreased miR-335-5p on endochondral ossification was evaluated by transfecting miR-335-5p mimics or miR-335-5p inhibitor in vitro in chondrocytes C28/I2. Finally, we injected the temporomandibular joint of rats intra-articularly with agomiR-335 in a unilateral anterior crossbite rat model to determine the in vivo regulation of miR-335. After the onset of temporomandibular joint osteoarthritis, miR-335-5p levels were gradually up-regulated, whereas endochondral ossification-related genes were down-regulated in condylar cartilage specimens. Our results showed that miR-335 inhibited endochondral ossification after administration of a miR-335 antagonist into the temporomandibular joint articular cavity of a unilateral anterior crossbite rat model. AgomiR-335, a miR-335 agonist, inhibited matrix mineralization in fibrocartilage stem cells in vitro and then miR-335-5p negatively regulated chondrocyte activity by directly targeting SP1 via promoting transforming growth factor-β/Smad signalling. miR-335-5p can significantly inhibit endochondral ossification; therefore, its inhibition may be beneficial for the treatment of temporomandibular joint osteoarthritis.

Measurement of Femoral Trochlear Morphology in Dogs Using Ultrasonography.

The aim of this study was to examine a method for measuring femoral trochlear morphology in dogs using ultrasonography, and survey femoral trochlear morphology in skeletally normal dogs. To examine the validity of ultrasonography, three raters measured the sulcus angle (SA; the angle between the medial and lateral facets) five times in five skeletally normal dogs. Intra- and interrater reliabilities were then calculated. We also calculated the correlation coefficient between SAs measured using ultrasonography and computed tomography (CT) or magnetic resonance imaging (MRI). Then, we surveyed the femoral trochlear morphology in skeletally normal dogs using ultrasonography. The intra- and interrater reliability for SAs measured using ultrasonography was good, and the correlation coefficient between SAs measured using ultrasonography and CT, or MRI, was strong. In skeletally normal dogs, the SAs for osseous contours decreased until 6 months of age. However, the SAs for cartilaginous contours did not change during the growth period. The ultrasonographic measurement method is reliable for the evaluation of femoral trochlear morphology in dogs. The contour of the articular cartilage surface of the femoral trochlea is already determined early in life, and ossification of the articular cartilage of the femoral trochlea proceeds until 6 months of age. The results of this study will provide crucial information for the evaluation of femoral trochlear morphology in dogs.

Curcumin-loaded porous scaffold: an anti-angiogenic approach to inhibit endochondral ossification

Bone marrow stem cells (BMSCs) are recognized for their robust proliferative capabilities and multidirectional differentiation potential. Ectopic endochondral ossification of BMSC-generated cartilage in subcutaneous environments is a concern associated with vascularization. Hence, devising a reliable strategy to inhibit vascularization is crucial. In this study, an anti-angiogenic drug, curcumin (Cur), was encapsulated into gelatin to create a porous Cur/Gelatin scaffold, with the aim of inhibiting vascular invasion and preventing endochondral ossification of BMSC-regenerated cartilage. In vitro wound healing tests demonstrated that a 30 μM Cur solution could inhibit the migration and growth of human umbilical vein endothelial cells without impeding BMSCs migration and growth. Compared to the gelatin scaffold, our findings verified that the Cur/Gelatin scaffold significantly inhibited vascular invasion after being subcutaneously implanted into rabbits for 12 weeks, as evidenced by gross observation and immunofluorescence CD31 staining. Moreover, both the porous gelatin and Cur/Gelatin scaffolds were populated with BMSCs and underwent in vitro chondrogenic cultivation to produce cartilage, followed by subcutaneous implantation in rabbits for 12 weeks. Histological examinations (including HE, Safranin-O/Fast Green, toluidine blue, and immunohistochemical COL II staining) revealed that the BMSC-generated cartilage in the gelatin group exhibited prominent endochondral ossification. In contrast, the BMSC-generated cartilage in the Cur/Gelatin group maintained cartilage features, such as cartilage matrix and lacunar structure. This study suggests that Cur-loaded scaffolds offer a reliable platform to inhibit endochondral ossification of BMSC-generated cartilage.

Assessment of thyroid cartilage ossification pattern in cancer patients: A suggestion of active ossification by tumor progression.

Ossified cartilage is much more susceptible to cancer infiltration, but the reason remains unknown, and the relationship between the ossification pattern and cancer infiltration has not been studied. The presence of thyroid cartilage ossification, cancer infiltration, ossification pattern (usual: direction from inferior to superior; unusual: other than the usual pattern), and distance between cancer and ossified cartilage were evaluated in laryngectomy specimens. There were 28 and 27 cases of usual and unusual patterns, respectively. There was no association between ossification pattern and cancer infiltration. However, the distance between the ossified area and cancer cells was greater in the usual pattern than in the unusual pattern (p = 0.006). And the usual pattern was more frequently observed in cases with a distance >1 mm than in cases with cancer infiltration or a distance ≤1 mm (p = 0.004). These results suggest the possibility of an active ossification due to tumor progression.

Environmentally relevant levels of BPA and NOR disturb early skeletal development in zebrafish

Bisphenol A (BPA) and fluoroquinolone antibiotics (FQs) have been detected frequently in aquatic environments. Studies have shown that high levels of BPA and FQs exposure have adverse effects on chondrogenesis in young terrestrial vertebrates. However, little is known about their combined toxicity to bone metabolism. Here, we evaluated the single and combined effects of BPA and norfloxacin (NOR, a typical species of FQs) at an environmentally relevant level (1 μg/L) on early skeletal development in zebrafish. We found that both individual and combined BPA and NOR exposure resulted in poor embryo quality and decreased calcium-phosphorus ratio. The malformation increased after exposure to BPA and NOR, and craniofacial cartilage ossification was delayed. At the molecular level, the transcriptions of genes related to ossification were down-regulated significantly, and the lysine oxidase activity decreased. Hence, we infer that an environmentally relevant concentration of BPA and NOR have adverse effects on early skeletal development in fish. In addition, combined exposure to BPA and NOR seems to have an antagonistic effect on early skeletal development.

Morphological and morphometric study of the scapulae of Korean wild deer

Korean water deer (Hydropotes inermis argyropus; Heude, 1884) and Siberian roe deer (Capreolus pygargus; Pallas, 1771) are Korean wild deer classified in the tribe Capreolini. C. pygargus in Korea were previously considered a single species; however, it was recently suggested that roe deer living on Jeju Island (Jeju roe deer; Capreolus pygargus jejuensis) is a distinct subspecies from roe deer living on the Korean peninsula (mainland roe deer; Capreolus pygargus tianschanicus) based on several studies demonstrating genetic and morphological features. In this study, we suggests that the scapular morphology and osteometric data can be used for interspecies discrmination between Korean wild deer. To compare the morphological characteristics of scapula among the three groups of deer, we analyzed the features and nine osteomorphological measurements of 31 H. i. argyropus (14 males and 17 females), 18 C. p. jejuensis (4 males and 14 females), and 23 C. p. tianschanicus (16 females and 7 males). The estimated ages of the deer were over 32–35 months. Data were analyzed by one-way repeated measures analysis of variance with post hoc Duncan test and discriminant functional analysis (DFA). H. i. argyropus and C. p. tianschanicus had the smallest and largest scapulae, respectively. The scapulae of the three Korean wild deer had a similar triangular shape, which was obscured by the tuber of the scapular spine, pointed acromion, broad infraspinous fossa, narrow supraspinous fossa, and partial ossification of scapular cartilage in older deer. H. i. argyropus had certain distinctive features, including a caudally pointed acromion, a notch between the supraglenoid tubercle and glenoid cavity (NBSG), a glenoid notch, and no sexual dimorphism, except for the longest dorsal length (Ld) and the scapular index (SI). C. p. jejuensis had a larger scapular index (SI) (61.74 ± 0.74%), compared with the SIs of H. i. argyropus and C. p. tianschanicus. The unique features of the scapula in C. p. jejuensis include its S-shaped cranial border. The C. p. jejuensis had a cranially pointed acromion, less frequent presence of glenoid notch and NBSG, short length of supraglenoid tubercle, and no sexual dimorphism. The C. p. tianschanicus had elevated cranial margin of the glenoid cavity, and frequent presence of glenoid notch and NBSG, similar to the H. i. argyropus. Similar to C. p. jejuensis, C. p. tianschanicus had a cranially pointed acromion. However, sexual dimorphism was observed in C. p. tianschanicus. DFA using osteometric data showed 97.22% of specimens were classified correctly into their species, meaning the osteometric parameters can be used for interspecies discrimination of Korean wild deer. Our findings indicate that the scapular morphologies of the three Korean wild deer have certain similarities and differences, suggesting that C. p. jejuensis are distinct from C. p. tianschanicus.

Plasma exosome miRNA-26b-3p derived from idiopathic short stature impairs longitudinal bone growth via the AKAP2/ERK1/2 axis

BackgroundCurrently, the etiology of idiopathic short stature (ISS) is still unclear. The poor understanding of the molecular mechanisms of ISS has largely restricted this strategy towards safe and effective clinical therapies.MethodsThe plasma exosomes of ISS children were co-cultured with normal human chondrocytes. The differential expression of exosome miRNA between ISS and normal children was identified via high-throughput microRNA sequencing and bioinformatics analysis. Immunohistochemistry, In situ hybridization, RT-qPCR, western blotting, luciferase expression, and gene overexpression and knockdown were performed to reveal the key signaling pathways that exosome miRNA of aberrant expression in ISS children impairs longitudinal bone growth.ResultsChondrocytes proliferation and endochondral ossification were suppressed after coculture of ISS plasma exosomes with human normal chondrocytes. High-throughput microRNA sequencing and RT-qPCR confirmed that plasma exosome miR-26b-3p was upregulated in ISS children. Meanwhile, exosome miRNA-26b-3p showed a high specificity and sensitivity in discriminating ISS from normal children. The rescue experiment showed that downregulation of miR-26b-3p obviously improved the repression of chondrocyte proliferation and endochondral ossification caused by ISS exosomes. Subsequently, miR-26b-3p overexpression inhibited chondrocyte proliferation and endochondral ossification once again. In situ hybridization confirmed the colocalization of miR-26b-3p with AKAP2 in chondrocytes. In vitro and in vivo assay revealed exosome miRNA-26b-3p impairs longitudinal bone growth via the AKAP2 /ERK1/2 axis.ConclusionsThis study is the first to confirm that miR-26b-3p overexpression in ISS plasma exosomes leads to disorders in proliferation and endochondral ossification of growth plate cartilage via inhibition of AKAP2/ERK1/2 axis, thereby inducing ISS. This study provides a new research direction for the etiology and pathology of ISS and a new idea for the biological treatment of ISS.Graphical

Identification and analysis of key microRNAs derived from osteoarthritis synovial fluid exosomes.

Identification and analysis of key microRNAs derived from osteoarthritis synovial fluid exosomes.

Fibroblast growth factor 9 reduces TBHP-induced oxidative stress in chondrocytes and diminishes mouse osteoarthritis by activating ERK/Nrf2 signaling pathway.

Osteoarthritis (OA) is a degenerative and progressive disease that affects joints. Pathologically, it is characterized by oxidative stress-mediated excessive chondrocyte apoptosis and mitochondrial dysfunction. Fibroblast growth factor 9 (FGF9) has been shown to exert antioxidant effects and prevent degenerative diseases by activating ERK-related signaling pathways. However, the mechanism of FGF9 in the pathogenesis of OA and its relationship with anti-oxidative stress and related pathways are unclear. In this study, mice with medial meniscus instability (DMM) were used as the in vivo model whereas TBHP-induced chondrocytes served as the in vitro model to explore the mechanism underlying the effects of FGF9 in OA and its association with anti-oxidative stress. Results showed that FGF9 reduced oxidative stress, apoptosis, and mitochondrial dysfunction in TBHP-treated chondrocytes and promoted the nuclear translocation of Nrf2 to activate the Nrf2/HO1 signaling pathway. Interestingly, silencing the Nrf2 gene or blocking the ERK signaling pathway abolished the antioxidant effects of FGF9. FGF9 treatment reduced joint space narrowing, cartilage ossification, and synovial thickening in the DMM model mice. In conclusion, the present findings demonstrate that FGF9 can inhibit TBHP-induced oxidative stress in chondrocytes through the ERK and Nrf2-HO1 signaling pathways and prevent the progression of OA in vivo.

超高精細CTを用いた喉頭軟骨の骨化についての検討

Purpose : Ossification of the laryngeal cartilage has been investigated, including the pattern of ossification, age-related changes, and sex differences. This study aimed to examine the beginning, the processes, and sex differences of ossification of the laryngeal cartilage in Japanese patients using ultra-high-resolution computed tomography (UHRCT).Materials and methods : A total of 47 cases were included in the present study (male, n=34 ; female, n=13). UHRCT was performed, and ossification of the laryngeal cartilage was visualized in three-dimensional (3D) images. Reconstructed images were evaluated the degree and process of ossification of laryngeal cartilage was compared between males and females in various age groups.Results : In both sexes, ossification of the thyroid cartilage started at less than 20 years of age. The pattern of thyroid cartilage began in the inferior horn, and spread upward in the superior horn and extended toward the midline along the inferior borders, ending at the lamina. The beginning part in cricoid cartilage was the cricoarytenoid joints, and that in arytenoid was muscular processes. On UHRCT, ossification of the laryngeal cartilage characteristically showed a “figure 8 of thyroid laminae” sign that was constructed by the paramedian bar and two rounded non-ossified areas.Conclusion : Ossification of the thyroid cartilage began at <20 years of age. The degree of ossification of the thyroid cartilage will increase with age ; however, the degree and frequency of the ossification in males greater in comparison to females. Three-dimensional images allowed the evaluation of ossification of the laryngeal cartilage.