Cell model of cartilage destruction in arthritis

Borrowing the description of medical encyclopedia "Arthritis refers to inflammatory diseases that occur in human joints and surrounding tissues. It can be divided into dozens. There are more than 100 million arthritis patients in China, and the number is increasing. The clinical manifestations are joints. Redness, swelling, heat, pain, dysfunction and joint deformity, severe joint disability, affecting the quality of life of patients."

Arthritis begins with chronic inflammation, but ultimately leads to dysfunction and key malformations. From the pathological changes, the disappearance of the cartilage layer is a very serious process. The field of tissue engineering research believes that cartilage formation is far more difficult to promote bone formation.

Look at the description of the medication in the medical encyclopedia.

Choose the appropriate treatment based on the type of arthritis, the characteristics of the symptoms, and the accompanying disease. The principle of treatment is early diagnosis and rational and combined use as soon as possible. Commonly used anti-rheumatic drugs are as follows:

1, non-steroidal anti-inflammatory drugs

It can inhibit the synthesis of prostaglandins and rapidly produce anti-inflammatory and analgesic effects. It has a good effect on relieving pain, but it can not change the course of the disease. Commonly used in clinical practice are ibuprofen, penicillamine, diclofenac, aspirin, indomethacin and the like.

2, cartilage protective agent

For example, glucosamine sulfate promotes the synthesis of cartilage, inhibits the decomposition of articular cartilage, and also has an anti-inflammatory effect. The sulfate rich in glucosamine sulfate itself is also one of the essential components of the synthetic cartilage matrix. These drugs can relieve pain symptoms and improve joint function. Long-term use (more than 2 years) can also delay the destruction of joint structure. Glucosamine sulfate has a slower onset of action, but it has good drug safety and is suitable for long-term use as a basic therapeutic drug.

3, slow acting anti-rheumatic drugs

Mostly used for rheumatoid arthritis and seronegative spondyloarthropathy. It has a certain control effect on the condition but it has a slower effect. Commonly used are gold mixture (intramuscular or oral), penicillamine, sulfasalazine, chloroquine and the like.

4, cytotoxic drugs

The immunosuppressive effect is produced by different routes. Commonly used are cyclophosphamide, methotrexate, Jin Duchun and so on. They are often second-line drugs for systemic lupus erythematosus, rheumatoid arthritis and vasculitis. The side effects are more and more serious, but they have a great effect on improving these diseases.

5, adrenocortical hormone

It is an anti-inflammatory and anti-allergic drug, which significantly improves the healing of connective tissue diseases such as systemic lupus erythematosus, but it cannot cure these diseases. Many of its side effects increase with increasing dose and prolonged treatment, so it should be carefully selected when measuring its efficacy and side effects.

6, antibiotics, etc.

Streptococcal infection can cause arthritis of rheumatic fever. The use of penicillin in the acute phase is the most effective drug to control streptococcal infection. Patients with acute rheumatic fever have long-term use of long-acting antibiotics to prevent the occurrence of long-term rheumatic carditis. For less than 5 years, children should be at least 18 years old. Tuberculous arthritis and fungal arthritis require active and effective anti-tuberculosis or antifungal treatment.

7, the treatment of gouty arthritis

Drug treatments including the acute phase include high-dose non-steroidal anti-inflammatory drugs or colchicine and uric acid-lowering treatment during remission. The uric acid-lowering drugs mainly include allopurinol which inhibits uric acid production and benzbromarone which promotes uric acid excretion.

Among the 7 drug types, 1, 3, 4, 5, and 7 are anti-inflammatory, 6 are anti-bacterial, and only 2 are cartilage protective.

For inflammation, whether the drug works fast or slow, it is short-term pain relief or long-term inhibition. At present, there are choices. However, in terms of cartilage protection, this is not the case. It is not important in this direction. Cartilage disappears and osteogenesis replaces it. It is disabling. It is not enough drug development.

However, in our research on the protection of cartilage damage by drugs, the primary cells of cartilage are difficult to operate. If the screening of new functional genes of drug mechanism is carried out on this cell, it is too difficult and the experiment is not reproducible. So what is the shortcut? Introduce a cell, SW1353. This strain of cells is a chondrosarcoma cell, which, although derived from a tumor, retains the characteristics of chondrocytes. The following is a study on the use of this cell as a model of chondrocyte, three articles.

Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes. Molecules. 2016.

This article is about the effects of compounds extracted from medicinal plants on immune cells and chondrocytes.

The chondrocytes used SW1353 and human normal knee joint primary chondrocytes. The description of SW1353 in this article is which are a substitute for primary human chondrocytes and an in vitro surrogate for osteoarthritic tissue. It can be used instead of primary chondrocytes for research. Look at the data.

Under the condition of using IL-1β as a stimulus, changes in genes related to inflammation and anabolism occurred in SW1353 after dosing.

Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway. Acta Pharmacologica Sinica. 2016.

This article examines the mechanism by which lidocaine causes chondrocyte apoptosis and Hyaluronan to protect cartilage.

The cells used SW1353 and primary cultured mouse chondrocytes. There are 7 pictures in total, the first 6 are made in SW1353, and the last one uses mouse primary cells. The idea of ​​this article is to take conclusions on the cell line, and finally verify it on the difficult primary cells.

The first picture is given, showing that Hyaluronan has no effect on chondrocyte proliferation, but can inhibit the killing effect of lidocaine on chondrocytes.

Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development. PNAS. 2013.

The finale is coming, PNAS article.

The role of the Notch signaling pathway in chondrocytes in cartilage ossification and bone and joint development was investigated.

The chondrocytes used human SW1353 and mouse ATDC5.

As can be seen from this figure, SW1353 is consistent with the ATDC5 phenotype. This experiment is very interesting. It is to connect the promoter of MMP13 or VEGFA to the front of luc, and then transfer different genes into the cell to see the effect of these genes on MMP13 and VEGFA. In fact, we can learn to find new functional genes. The expression of classical molecules was used as a detection index, and the promoter of the classical molecule was constructed in front of luc to construct a stable strain. Then, high-throughput function screening is performed to analyze the genes that may be related in the early stage and operate in this stable strain. The change of luc is used to evaluate whether the gene function is related to the classical molecule, and the classical molecular change represents the disease.

In the next article, we share research on synovial cells in arthritis.

PS: I hope that friends who have more exchanges with Jibo in learning and experimentation can pay attention to Jikai Gene WeChat and reply to the words “Jibo”.


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