SHP2 inhibition attenuates osteoarthritis by maintaining homeostasis of cartilage metabolism via the DOK1/UPP1/uridine cascade

Osteoarthritis (OA) is a degenerative joint disease that is characterized by increasing loss of cartilage, remodeling of the periarticular bone, and inflammation of the synovial membrane. Besides the common OA therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the treatment with chondroprotectives, such as glucosamine sulfate, chondroitin sulfate, hyaluronic acid, collagen hydrolysate, or nutrients, such as antioxidants and omega-3 fatty acids is a promising therapeutic approach. Numerous clinical studies have demonstrated that the targeted administration of selected micronutrients leads to a more effective reduction of OA symptoms, with less adverse events. Their chondroprotective action can be explained by a dual mechanism: (1) as basic components of cartilage and synovial fluid, they stimulate the anabolic process of the cartilage metabolism; (2) their anti-inflammatory action can delay many inflammation-induced catabolic processes in the cartilage. These two mechanisms are able to slow the progression of cartilage destruction and may help to regenerate the joint structure, leading to reduced pain and increased mobility of the affected joint.

Download Full-text

The Effect of Irrigation Solution at Different Temperatures on Articular Cartilage Metabolism

Arthroscopy The Journal of Arthroscopic and Related Surgery ◽

10.1016/j.arthro.2010.10.019 ◽

2011 ◽

Vol 27 (4) ◽

pp. 526-531 ◽

Cited By ~ 18

Author(s):

Baris Kocaoglu ◽

James Martin ◽

Brian Wolf ◽

Mustafa Karahan ◽

Annunziato Amendola

Keyword(s):

Articular Cartilage ◽

Cartilage Metabolism ◽

Different Temperatures ◽

Irrigation Solution

Download Full-text

Biomarkers of Cartilage Metabolism and IGF-1 as Influenced by Dietary Starch

Journal of Equine Veterinary Science ◽

10.1016/j.jevs.2009.04.098 ◽

2009 ◽

Vol 29 (5) ◽

pp. 397-398 ◽

Cited By ~ 1

Author(s):

E.A. Nowelsky∗ ◽

J.K. Morrissey ◽

E.A. Jedrzejewski ◽

P.A. Harris ◽

W.B. Staniar

Keyword(s):

Cartilage Metabolism ◽

Dietary Starch

Download Full-text

Effect of steroids on cartilage metabolism "in vitro"

Acta Endocrinologica ◽

10.1530/acta.0.112s035 ◽

1986 ◽

Vol 113 (4_Suppl) ◽

pp. S35-S40 ◽

Cited By ~ 4

Author(s):

Marc V.L. DU CAJU ◽

Raoul P. ROOMAN

Keyword(s):

Growth Factor ◽

Thymidine Incorporation ◽

Normal Serum ◽

Synthetic Analogue ◽

Factor Activity ◽

Poor Growth ◽

Cartilage Metabolism ◽

Glucocorticoid Administration

ABSTRACT Conditions characterized by high levels of glucocorticoids are associated with poor growth. Serum somatomedin or insulin-like growth factor activity measured by cartilage bioassay systems is low, but is generally not accompanied by a fall in somatomedin concentration. Hydrocortisone and a synthetic analogue, dexamethasone, impaired the serum stimulated "in vitro" 35S sulphate and 3H-thymidine incorporation in porcine rib cartilage at physiological concentrations. Hydrocortisone added at a concentration of 0,1 μg/ml decreased the potency of normal serum to 50 % of controls. Dexamethasone was at least 10 times more potent. Removal of "in vitro" or "in vivo" administered hydrocortisone with dextran-coated charcoal restored the sulphate and thymidine activity to normal. We conclude that physiological amounts of glucocorticoids inhibit the "in vitro" porcine cartilage metabolism. Glucocorticoid administration "in vivo" does not abolish the activity of the cartilage stimulating effect of serum but affects cartilage metabolism directly or by the induction of locally produced inhibitors of cartilage metabolism.

Download Full-text