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*

The changes of hyaline articular cartilage from rabbits after air exposure were evaluated. The knee joints were exposed to air for periods of thirty minutes to two hours. The animals were killed periodically, at three days, one week and three weeks postoperatively. After sacrifice, the cartilage was removed and prepared for study by light microscopy and electron microscopy. Exposure to room air for thirty minutes produced chondrocyte necrosis in the upper third of the cartilage, and exposure for 60 minutes or longer produced chondrocyte necrosis of the entire thickness of articular cartilage at three days after arthrotomy. But, three weeks after arthrotomy, we could not find any chondrocyte necrosis in any rabbits at varying periods of air exposure. There was no significant change in proteoglycan content between the aired and control cartilage. Clinical Relevance: Exposing cartilage to air can cause transient and reversible cartilage damage. If these changes are not reversible, the orthopedic surgeon should consider avoiding the prolonged exposure of articular cartilage to air, since complete matrix disintegration is known to occur months after chondrocyte necrosis.
*Air ; Animal ; Cartilage, Articular/metabolism/*pathology/ultrastructure ; Hyalin/*metabolism ; Microscopy, Electron ; Necrosis ; Rabbits ; Time Factors

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

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

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

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is a disease of the elderly and extremely rare in young individuals. If young people develop CPPD crystal deposition disease, it may be associated with metabolic diseases such as hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's disease, hypothyroidism, gout, acromegaly, and X-linked hypophosphatemic rickets. Therefore, in young-onset polyarticular CPPD crystal deposition disease, investigation for predisposing metabolic conditions is warranted. We report a case of a young male patient with idiopathic CPPD crystal deposition disease, who did not have any evidences of metabolic diseases after thorough evaluations. As far as we know, this is the first report of a young male patient presented with idiopathic CPPD crystal deposition disease.
Adult ; Calcium Pyrophosphate/*metabolism ; Cartilage, Articular/metabolism/pathology ; Diagnosis, Differential ; Human ; Knee Joint/*pathology ; Male ; Metabolic Diseases/metabolism/pathology ; Shoulder Joint/pathology

OBJECTIVETo look into the character of the expression of collagen type II and transforming growth factor beta1 (TGF-beta1), basic fibroblast growth factor (bFGF) in the apical articular process cartilages of adolescent idiopathic scoliosis (AIS) and congenital scoliosis (CS) patients.

METHODSThe articular processes of 22 AIS and 18 CS were collected. The techniques of HE staining, immunohistochemistry and in situ hybridization were adopted in this research. By comparing the apical processes with the end processes, the convex processes with the concave processes, the AIS processes with CS processes, the pathological changes of the articular process cartilages of these patients and the distribution of collagen type II and TGF-beta1, bFGF in them were studied. The images of immunohistochemistry and in situ hybridization were input into the image analysis system and were analyzed semi-quantitatively. The SAS software (8.01) was adopted, and P < 0.05 was defined as the significant level.

RESULTSThe expression of collagen type II and TGF-beta1, bFGF in AIS was similar to CS: the concave sides of apexes were higher than the convex sides. The comparisons had statistical significance. There was no statistical significance between upper and lower end vertebrae in convex and concave sides, between convex and concave sides in upper and lower end vertebrae. The apical vertebrae were significantly higher than the ipsilateral sides of upper or lower end vertebrae for collagen type II. There was no statistical difference of the expression at the concave, convex, upper, lower end vertebrae between AIS and CS.

CONCLUSIONSThe cartilages of the apical processes show some signs of regression and hypoplasia in scoliosis. The concave side is more severe than the convex side. Increase of collagen type II and TGF-beta1, bFGF in the concave sides of apical processes in scoliosis may be the results of reconstruction of extracellular matrix and the compensation reactions which are caused by abnormal biomechanical forces such as compressive stresses. Compressive stress on the concave sides has more influences on the expression of collagen type II than tensile stress on the convex sides.

Adolescent ; Cartilage, Articular ; metabolism ; pathology ; Child ; Collagen Type II ; metabolism ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Scoliosis ; metabolism ; pathology ; Transforming Growth Factor beta1 ; metabolism

Chondroblastoma ; pathology ; Chondroma ; pathology ; Chondrosarcoma ; metabolism ; pathology ; surgery ; Cricoid Cartilage ; Diagnosis, Differential ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; surgery ; Laryngectomy ; Lymph Node Excision ; Male ; Middle Aged ; Osteoblastoma ; pathology ; Osteosarcoma ; pathology ; S100 Proteins ; metabolism ; Sarcoma, Clear Cell ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

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