The Wnt signaling exists in every kinds of species and regulates a variety of biological processes including cell fate, proliferation and function, immunity, stress, apoptosis and so on. During the researching, Wnt signaling also plays an important role in chondrocyte differentiation and maturation. So it has been the new spot in pathogenesis of osteoarthritis study.
Animals ; Chondrocytes ; metabolism ; pathology ; Humans ; Osteoarthritis ; metabolism ; pathology ; Signal Transduction ; Wnt Proteins ; metabolism

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage loss and accounts for a major source of pain and disability worldwide. However, effective strategies for cartilage repair are lacking, and patients with advanced OA usually need joint replacement. Better comprehending OA pathogenesis may lead to transformative therapeutics. Recently studies have reported that exosomes act as a new means of cell-to-cell communication by delivering multiple bioactive molecules to create a particular microenvironment that tunes cartilage behavior. Specifically, exosome cargos, such as noncoding RNAs (ncRNAs) and proteins, play a crucial role in OA progression by regulating the proliferation, apoptosis, autophagy, and inflammatory response of joint cells, rendering them promising candidates for OA monitoring and treatment. This review systematically summarizes the current insight regarding the biogenesis and function of exosomes and their potential as therapeutic tools targeting cell-to-cell communication in OA, suggesting new realms to improve OA management.
Apoptosis ; Cartilage/pathology* ; Cartilage, Articular/metabolism* ; Cell Communication ; Chondrocytes/metabolism* ; Exosomes/pathology* ; Humans ; Osteoarthritis/therapy*

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Aggrecans/metabolism* ; Animals ; Cartilage, Articular/metabolism* ; Chondrocytes/pathology* ; Cytoskeletal Proteins/metabolism* ; Mice ; Muscle Proteins/metabolism* ; Osteoarthritis/pathology* ; Temporomandibular Joint/pathology*

OBJECTIVETo investigate the gene expression and potential functions of transforming growth factor-beta1 in osteophyte development.

METHODSA total of 25 specimens were obtained from individuals undergoing total knee arthroplasty due to severe primary osteoarthritis. Tissue samples were embedded in paraffin wax and made into sections. Hematoxylin and eosin and toluidine blue stainings were performed. The expressions of collagen I, IIa, IIb, and X were detected by immunohistochemistry. Based on the histomorphology of cellularity and matrix abundance, the glycosaminoglycans content, and the differential expressions of collagen I, IIa, IIb, and X, the osteophytic tissues were classified. For each different type of osteophyte, expressions of transforming growth factor-beta1 were detected by immunohistochemistry and in situ hybridization, and results were analyzed using the image analysis system.

RESULTSFive different types of osteophytes were identified as type I, type II, type III, type IV, and type V. Transforming growth factor-beta1 mRNA was more and intensely expressed in chondrocytes of type II and III osteophytes, and was less in other types of osteophytes. The difference was significant (P<0.05, P<0.01).

CONCLUSIONTransforming growth factor-beta1 mRNA is mainly expressed in early-mid stages of osteophytes and may play an important role in promoting the proliferation and differentiation of chondrocytes in the early stages of osteophyte development.

Chondrocytes ; metabolism ; pathology ; Humans ; Osteoarthritis, Knee ; metabolism ; pathology ; Osteophyte ; metabolism ; pathology ; RNA, Messenger ; biosynthesis ; Transforming Growth Factor beta1 ; biosynthesis ; genetics

OBJECTIVETo explore the effects of selenium and/or iodine deficiency on chondrocyte apoptosis in articular cartilage in rats.

METHODSForty-eight Sprague-Dawley rats were randomly divided into selenium deficiency group, iodine deficiency group, combined selenium and iodine deficiency group, and control group. Chondrocyte apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and Bcl-2 and Bax in articular cartilage were stained by immunohistochemistry in F3 generation of rats.

RESULTSIn articular cartilage, the positive rate of apoptotic chondrocytes stained by TUNEL in the upper and middle zones in selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05) were significantly higher than that in control group. The apoptotic chondrocytes were prominent in the middle zone. The positive percentage of chondrocytes apoptosis was not significantly different among these three groups (P > 0.05). Compared with the control group, the expressions of both Bcl-2 and Bax were significantly higher in the upper and middle zone in the selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05); however, the expressions of Bcl-2 and Bax were not significantly different among these three groups (P > 0.05).

CONCLUSIONSelenium and/or iodine deficiency may induce chondrocyte apoptosis.

Animals ; Apoptosis ; Cartilage, Articular ; metabolism ; pathology ; Chondrocytes ; metabolism ; pathology ; Female ; Iodine ; deficiency ; Male ; Rats ; Rats, Sprague-Dawley ; Selenium ; deficiency

Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target.
Cartilage/metabolism/pathology ; Case-Control Studies ; Cell Line ; Chondrocytes/*metabolism/pathology ; Growth Differentiation Factor 5/genetics/*metabolism ; Humans ; MicroRNAs/genetics/*metabolism ; Osteoarthritis/*metabolism/pathology ; Up-Regulation

Osteoarthritis (OA) is a kind of degenerative disease characterized by hyperosteogeny at the joint margins and articular cartilage degeneration. Mechanical stress can regulate the multiple functions of cells. The integrin as one of the mechanoreceptors on the surface of cells, mainly mediated adhesion between cells and extracellular matrix, which plays an important role in the mechanical signal transmission to regulate the physiological functions of cell. Therefore, it is very important to select proper mechanical stimulation (such as naprapathy) in the early and middle stage of osteoarthritis, which regulate the expression of integrins to affect the function of chondrocytes, repair the damaged chondrocyte and delay the articular cartilage degeneration.
Animals ; Biomechanical Phenomena ; Chondrocytes ; cytology ; metabolism ; pathology ; Gene Expression Regulation ; Humans ; Integrins ; metabolism ; Mechanical Phenomena ; Protein Subunits ; metabolism

OBJECTIVETo observe the morphology and phenotypes of cells extracted from the endplate in the intervertebral discs and identify the factors affecting their biological characteristic.

METHODSThe intervertebral disc endplate were digested enzymatically, and the morphology of the obtained cells was examined under light microscope. Immunhistochemical analysis of collagen II and real-time PCR was carried out, and the morphologies, viability, cell growth, apoptosis and chondrocyte matrix production were compared between the cells isolated from the degenerative and normal vertebral endplates.

RESULTSThe cells in primary culture presented with spherical and oval morphology, and the cytoplasm was stained blue with toluidine blue. The morphologies of the cartilage endplate cells and the articular cells were almost identical. All the freshly isolated cells expressed collagen II. The degenerative vertebral endplate cells showed decreased expression of collagen II with increased apoptotic cells as compared with normal vertebral endplate cells.

CONCLUSIONThe intervertebral disc endplate cells, like articular cartilage cells, express cartilage-specific matrix proteins. Degenerative vertebral endplate cells show decreased cell vitality with increases cell apoptosis.

Adult ; Apoptosis ; physiology ; Cartilage ; metabolism ; pathology ; Cells, Cultured ; Chondrocytes ; metabolism ; pathology ; Collagen ; metabolism ; Female ; Growth Plate ; metabolism ; pathology ; Humans ; Intervertebral Disc ; metabolism ; pathology ; Intervertebral Disc Degeneration ; metabolism ; pathology ; Lumbar Vertebrae ; metabolism ; pathology ; Male ; Young Adult

OBJECTIVETo study the characteristics of cellular metabolism of mandibular condylar chondrocytes in repairing state of osteoarthrosis and investigate its role in the pathogenesis of the disease.

METHODSTemporomandibular joint osteoarthrosis model of rabbits was created by the partial resection of joint disc and confirmed with histological diagnosis. The chondrocytes were harvested from osteoarthritic condylar cartilage in the repairing state and cultured in vitro under the monolayer culture condition. The cellular expression of cartilaginous matrix protein, collagenase and growth factors between the osteoarthritic chondrocytes and the normal controls were measured with RT-PCR technique to outline the basic feature of the osteoarthritic cells.

RESULTSThe cultured cells were confirmed as chondrocytes with their ability of expression of collagen type II and Aggrecan. In the reactive repairing state of osteoarthrosis, the chondrocytes showed the imbalance of expression of ECM proteins, and increased expression of collagenase and endogenous growth factors such as IGF-1 and TGF-beta1.

CONCLUSIONSThis study found the active anabolism of the chondrocytes within the osteoarthritic condylar cartilage and the imbalance synthesis of cartilage matrix. These repairing attempts by the osteoarthritic chondrocytes may be impossible to restore the primary homeostasis within the condylar cartilage.

Animals ; Cartilage, Articular ; metabolism ; pathology ; Cells, Cultured ; Chondrocytes ; metabolism ; Extracellular Matrix ; genetics ; metabolism ; Male ; Mandibular Condyle ; metabolism ; pathology ; Osteoarthritis ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rabbits ; Temporomandibular Joint Disc ; pathology ; Temporomandibular Joint Disorders ; metabolism ; pathology

OBJECTIVETo investigate the effects of excessive intake of fluoride on the expression of type II collagen gene and types and morphological change of collagen fiber in the bone tissues of rats.

METHODSA rat model with fluorosis was established by adding 221 mg/L of sodium fluoride (NaF) to drinking water for the rats for 15 days, 30 days and two months, respectively. Type II collagen alpha1 (II) cDNA probe was prepared, and cDNA-mRNA in-situ hybridization was employed to detect change in expression of type II collagen mRNA in the bone tissues of rats with excessive intake of fluoride (221 mg/L NaF). Picrosirius-polarization method was used to observe types of collagen and morphology of collagen fiber in the bone tissues.

RESULTSChondroblasts were found in the femur and other bone tissues of the rats after exposure to fluoride. cDNA-mRNA in-situ hybridization showed that expression of type II collagen gene could be observed in the cytoplasm of chondrocytic lacuna and chondrified bone tissues. mRNA in collagen of chondrocytes of the rib cartilage reached the peak level 15 days after exposure to fluoride, and decreased gradually one month and two months after exposure. Polychromatic type II collagen, breakage of collagen fiber, disorder array and reduced content of type II collagen could be found in the bone tissues with picrosirius-polarization method.

CONCLUSIONSExcessive intake of fluoride could lead to changes in types and structure of collagen (cross-linkage) of bone tissues, which caused expression of type II collagen gene in the chondrified bone tissues and enhanced its expression in the rib cartilage tissues.

Animals ; Bone Diseases ; metabolism ; pathology ; Chondrocytes ; metabolism ; Collagen Type II ; biosynthesis ; genetics ; Fluoride Poisoning ; genetics ; metabolism ; pathology ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar