OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and the incidence of congenital heart disease is also high. The pathogenesis behind PCD is that gene variants cause structural or functional disorders of respiratory cilia and motile cilia of other organs, leading to a series of heterogeneous clinical manifestations, which makes it difficult to identify and diagnose PCD. Combining different disease screening tools and understanding the relationship between genotypes and phenotypes may facilitate early diagnosis and treatment for PCD.
Chronic Disease ; Cilia/pathology* ; Humans ; Kartagener Syndrome/genetics* ; Phenotype ; Sinusitis

OBJECTIVETo analyze the clinical characteristic of Kartagener syndrome in Chinese and foreign children.

METHODFour cases of Kartagener syndrome diagnosed in our hospital were analyzed with literature review. The differences between Chinese and foreign children in clinical manifestations and diagnosis were compared.

RESULTAll of the cases had the following clinical manifestations: recurrent productive cough, nasosinusitis, dextrocardia, total situs inversus and bronchiectasia. Situs inversus of the airway structure was visible under the bronchoscope, and electron microscopy of the respiratory mucosa showed an abnormal ciliary ultrastructure. By using "Kartagener syndrome" and "child" as the key words, reports on 55 Chinese cases and 61 foreign cases in children were retrieved from CNKI and PubMed databases. The average age of diagnosis was 9.16 ± 3.67 years in China, which was significantly later than 7.07 ± 4.92 years in foreign countries (t=2.642, P<0.01). The main clinical manifestations were recurrent productive cough, nasosinusitis or rhinopolyp, recurrent pulmonary infection, recurrent wheezing and otitis media. Sinus imaging showed maxillary sinusitis. Dextrocardia, total situs inversus and bronchiectasia were found on thoracic and abdominal CT. The ciliary ultrastructural analysis showed shorter and missing dynein arm (6/6 cases in China and 25/27 cases in foreign) .

CONCLUSIONThe clinical manifestations are recurrent upper and lower respiratory tract infection combined with dextrocardia or other situs inversus in both China and other countries. The diagnosis abroad relied more on abnormal ciliary ultrastructure observed under electron microscopy, but in China mainly relied on its typical clinical manifestations.

Asian Continental Ancestry Group ; Child ; China ; Cilia ; ultrastructure ; Humans ; Kartagener Syndrome ; diagnosis ; ethnology ; Lung ; pathology ; ultrastructure ; Microscopy, Electron ; Respiratory Tract Infections ; diagnosis ; Situs Inversus ; diagnosis

OBJECTIVE: To investigate the ultrastructural changes of the mucosa of eustachian tube in mice and to reveals the influence of eustachian tube on middle ear function and its relavence with otitis media. METHOD: 12 wild type and 12 mutant mice were divided into two groups by age to observe the the ultrastructural changes of the mucosa of eustachian tube. RESULT: Wild type mice exhibited a thick lawn of morphologically normal, distributed cilia in the mucosa of the middle ear at both time points. The cilia of mucosa of middle ear in mutant mice were short, impaired and disrupted. The impairment of the cilia progressed to a much great severity at 6 months compared to 3 months. CONCLUSION Otitis media occurs not only the ciliated cells decreased and the goblet cells increased. More importantly, the ciliary structure was damaged, leading to the dysfunction of the mucociliary transport system and causing otitis media.
Animals ; Cilia ; pathology ; ultrastructure ; Disease Models, Animal ; Ear, Middle ; pathology ; Eustachian Tube ; pathology ; ultrastructure ; Goblet Cells ; Mice ; Microscopy, Electron, Scanning ; Mucociliary Clearance ; Mucous Membrane ; pathology ; ultrastructure ; Otitis Media ; pathology

Cilia ; pathology ; Endometrial Hyperplasia ; complications ; pathology ; Endometrial Neoplasms ; complications ; pathology ; Endometrium ; pathology ; Fallopian Tubes ; pathology ; Female ; Humans ; Metaplasia ; classification ; complications ; pathology

OBJECTIVE: To observe ultrastructure of maxillary sinus mucosa of experimental acute sinusitis in rabbits. METHOD: Twenty-five rabbits were randomly divided into experimental group (20 rabbits) and blank control group (5 rabbits). We established a rhinogenic model of experimental acute sinusitis in experimental group. Five rabbits chosen randomly in experimental group were sacrificed and dissected after 1, 2, 3, and 4 weeks, and the tissue (0.3 cm x 0.3 cm) of sinus mucosa were prepared for visualization by transmission electron microscope (TEM). Animals in blank control group were sacrificed after 1 week. RESULT: Under the transmission electron microscope, in the blank control group, cilia of maxillary sinus mucosa lined up in order without ciliary loss, no stretched endoplasmic reticulum or turgescent mitochondria was observed. However, in the experimental group, inordinate array and loss of cilia was observed, a few compound cilia and cytoplasmic protrusion were also found. Both endoplasmic reticulum and mitochondria were swelling, and the lymphocytes were infiltrating with fibroblast proliferation in the submucosa. There was statistically significant difference between the experimental group and the blank control group (P < 0.05). In the experimental group, the number of compound cilia increased from 1 to 4 weeks, and the amount of compound cilia of the mucosa at 3 and 4 weeks was significantly higher than that at 1 week (P < 0.05). Swelling of mitochondria and endoplasmic reticulum was severe at 2 weeks and abated gradually with time, the results at 2 weeks were different from those of experimental group at 4 weeks (P < 0.05). CONCLUSION The obstruction of nasal sinuses and the bacterial infection might lead to ultrastructural changes of maxillary sinus mucosa, and these ultrastructural changes were believed to the important processes of pathological changes in acute sinusitis.
Acute Disease ; Animals ; Cilia ; ultrastructure ; Maxillary Sinus ; ultrastructure ; Maxillary Sinusitis ; pathology ; Microscopy, Electron, Scanning Transmission ; Mucous Membrane ; ultrastructure ; Rabbits ; Sinusitis ; pathology

OBJECTIVE: To investigate the effects of intranasal steroid on nasal mucosa in rat model of allergic rhinitis (AR). METHOD: Thirty-six SD rats were randomly divided into three groups (each included 12 rats): the intranasal steroid group(group A),the allergic rhinitis group(group B) and the normal control group(group C). AR model was reproduced by ovalbumin in group A and B. The control group was allergized by NS instead of ovalbumin. Group A was used steroid spray in nasal and Group B and C was used normal saline. Then ,after the last provocation,the allergic symptoms were evaluated,the number of eosinophil (EOS) of the rats' nasal mucosa was counted under hematoxylineosin staining and the goblet cells was counted under alcian blue-periodic acid-Schiff staining. The morphological changes of the rats' nasal mucosa were observed by scanning electron microscope. RESULT: Compared with group B,the inhibition of nasal symptoms was found after used of steroid spray in group A. The EOS and the goblet cells in group A was significantly different with that in Group B (P < 0.05), but no significant differences compared with group C (P > 0.05). Observed by scanning electron microscope, the cilia of the epithelium in group B were significantly lodging, disoriented, winding and secreting,while the cilia of the epithelium in Group A and C had similar appearance. CONCLUSION Intranasal steroid spray can relieve symptoms and inflammatory conditions of nasal mucosa in allergic rhinitis, and can repair injured nasal mucosa cilia.
Androstadienes ; pharmacology ; Animals ; Anti-Inflammatory Agents ; pharmacology ; Cilia ; ultrastructure ; Disease Models, Animal ; Inflammation ; Nasal Mucosa ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic, Perennial ; drug therapy ; pathology

One of the most widespread cellular organelles in nature is cilium, which is found in many unicellular and multicellular organisms. Formerly thought to be a mostly vestigial organelle, the cilium has been discovered in the past several decades to play critical motile and sensory roles involved in normal organogenesis during development. The role of cilia has also been implicated in an ever increasing array of seemingly unrelated human diseases, including blindness, kidney cysts, neural tube defects and obesity. In this article we review some of the recent developments in research on cilia, and how defects in ciliogenesis and function can give rise to developmental disorders and disease.
Abnormalities, Multiple ; pathology ; Animals ; Cerebellar Diseases ; genetics ; pathology ; Cilia ; physiology ; ultrastructure ; Flagella ; physiology ; Hedgehog Proteins ; metabolism ; Humans ; Models, Animal ; Polycystic Kidney Diseases ; pathology ; Protein Transport ; Signal Transduction ; Wnt Proteins ; metabolism

OBJECTIVE: To characterize explore the feature of nasal mucosa ultrastructure changes after prolonged allergen challenge and to examine the relationships between nasal airway hyperresponsivity and ultrastructure ciliates changing. METHOD: We prepared rat allergic rhinitis for ovalbumin. Rats were subsequently challenged two times a week with ovalbumin from day 16 to day 42, 56, 112 and 140. We examined allergen-induced nasal symptoms and objective nasal symptoms using evaluation of symptoms and EOS. Moreover, the pathologic changes were investigated after allergen challenge. RESULT: The extended allergen challenge protocol caused significant nasal ultrastructure changing. Specifically, ultrastructure changing were characterized by disordered Ciliated cells and some sticky integrated, dumping of epithelium ciliates, even some loss. Allergen-induced nasal symptoms were first increased but gradually decreased in nasal symptoms after prolonged allergen challenge. CONCLUSION We have demonstrated that ultrastructure changes of nasal mucosa ciliates in a rat allergic rhinitis model prolonged allergen exposure. Moreover, prolonged allergen exposure induced a reduction of nasal symptoms together with a progression of nasal mucosa ciliates damaging.
Animals ; Cilia ; ultrastructure ; Female ; Male ; Nasal Mucosa ; pathology ; ultrastructure ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic, Perennial ; pathology

Duplication is a rare congenital abnormality and may occur in any region of the gastrointestinal tract. A 19-year-old woman was admitted due to lower abdominal pain. Abdomino-pelvic CT scan showed a cystic mass interpreted as mesenteric cyst or duplication cyst. On the operation finding, it seemed to be arised from mesentery but attached to the ileum. Microscopically, the cystic wall was lined by non-keratinizing squamous, ciliated pseudostratified columnar epithelium, and ectopic gastric mucosa with two distinct muscular layers and a serosa. We report the first case of ileal duplication cyst lined by squamous and ciliated columnar epithelium in Korea.
Cilia/pathology ; Cysts/*congenital/pathology/radiography ; Epithelium/pathology ; Female ; Humans ; Ileal Diseases/*diagnosis/pathology/radiography ; Ileum/*abnormalities/pathology ; Tomography, X-Ray Computed ; Young Adult