Cartilage metabolism Product details

Hyaluronic Acid-Hyaluronan (HA)

Fasting blood collection. Serum or EDTA Plasma stable for 72 hours at 2–8 °C, 6 months at -20°C, longer storage at -80°C. Maximum 3 freeze- and thaw cycles.

Hyaluronic Acid Values are dependent on age and gender and influenced by food intake and physical activity.
Values in EDTA-Plasma are 18 % lower.

Clinically Healthy Subjects n=53 between 16 and 79 years.
36.7 ± 23.5 ng/ml.

Human, dog, horse, rat and other animal models

Hyaluronan
Hyaluronan, also known as hyaluronic acid (HA) or hyaluronate is a large linear non-sulfated glycosaminoglycan (GAG) with a molecular weight between10/6 and 10/7 Da. It is a major component of connective tissues and thus distributed ubiquitously in the organism. About one-half of the body’s entire hyaluronan is found in the skin and about one fourth in the skeleton and its supporting structures like ligaments and joints. Hyaluronan is synthesized by fibroblasts and other specialized connective tissue cells. Hyaluronan is especially important for the structure and organization of extracellular matrices. The hyaluronan network acts as an osmotic buffer and is reponsible for water homeostasis as well as it regulates protein distribution via the formation of flow and diffusion barriers. Additionally, hyaluronan interacts with proteins and cell surfaces and thus has a strong influence on cell proliferation, differentiation and tissue repair.
Turnover and catabolism
The tissue half-life of hyaluronan differs between species and varies from about one to several days. A certain amount of hyaluronan is degraded locally but the much larger part is removed and degraded by the lymphatic system. The remainder enters the blood circulation from where it is removed primarily by liver endothelial cells. A minor part is metabolized by the kidneys and the spleen. Adult cartilage takes a special position, since it is avascular and depends upon the synovial fluid providing its nutrition as well as the disposal of metabolic wastes. Thus, hyaluronan resulting from cartilage degradation is firstly released into the synovial fluid from where it enters the blood and lymph stream respectively through the highly vascularized synovial membrane. The serological half-live of hyaluronan is about 2 - 5 minutes. The normal adult human serological level of hyaluronan varies between 10 and 100 micrograms/l and the total hyaluronan turnover in serum is estimated to be in the range of 10 - 100 mg/24 h. Serum hyaluronan is influenced by various factors including age, sex and ethnicity as well as food intake and the level of physical activity. Increased serum levels were found either due to an excessive synthesis of hyaluronan (e.g. joint or skin disease, cancer) or due to a decreased hepatic clearance (liver fibrosis/cirrhosis). Hereditary diseases with disturbances of the hyaluronan metabolism (e.g. Werner’s syndrome (Pangeria) or Acrogeria) are rare and characterized by accelerated or premature aging. Subnormal hyaluronan tissue levels in combination with increased serum and urinary levels indicate an increased hyaluronan turnover in concerned persons. Certain malignancies e.g. mesothelioma and Wilms’ tumor are able to produce either hyaluronan or factors which affect other cells to produce hyaluronan and are thus accompanied by high hyaluronan serum levels. Increased serum levels of hyaluronan could be seen in inflammatory processes like psoriasis or sclerosis and also during septic conditions.
Therapeutic application
One of the first application areas for hyaluronan was the ophtalmic surgery where it acts as a moisturizer to protect sensitive eye tissue and to enhance wound healing. Intra-articular injections of hyaluronan are able to relieve knee pain in horses and man. Further therapeutic applications focus on tissues naturally showing high amounts of hyaluronan like the skin or cartilage. Tissue engineering research utilizes hyaluronan as scaffold and drug carrier for implants or wound dressings to enhance wound healing. In plastic surgery hyaluronan is used as injectable soft tissue filler.

Hyaluronan as a diagnostic marker
Joint disease
Hyaluronan is a main component of the cartilage matrix as well as the synovial fluid. Its viscoelastic properties are responsible for a proper joint function. Proliferative synovial inflammation - which is a key feature of rheumatoid arthritis (RA) - causes the forced synthesis of hyaluronan increasing both the synovial and serological level of hyaluronan. However, joint inflammation might also occur during other types of joint diseases, e.g. osteoarthritis (OA) or traumatic injury. In RA and OA patients the concentration of hyaluronan correlates with the degree of joint inflammation and synovial proliferation as well as with the degree of joint space narrowing. Patients with higher initial values showed a more progressive course of disease. Serum hyaluronan could therefore be used to detect degenerative joint disease and to monitor disease progression as well as to judge the success of appropriate therapies. However, increased hyaluronan levels might indicate both forced hyaluronan synthesis due to synovial inflammation and progressive cartilage degradation. Thus, hyaluronan values should be always matched with parallely collected results like clinical or radiographic findings to clarify the disease focus. Since RA patients show markedly increased hyaluronan concentrations 0.5 - 2 hours after leaving bed corresponding with the a decrease in joint stiffness, valuable information might be obtained by sampling during the morning hours in these patients.
Liver disease
As a result of permanent inflammation most chronic liver diseases are characterised by fibrosis and cirrhosis causing a decreased capacity for hyaluronan clearance. The leading causes of chronic liver disease are viral infection (hepatitis B or C), and alcohol abuse. Patients with extensive liver fibrosis and cirrhosis show markedly increased serum levels of hyaluronan with the progression of liver fibrosis being associated with an increase of serum hyaluronan. Serum hyaluronan could therefore be used to monitor patients with the risk of progressive fibrosis, as well as to judge the success of antifibrotic therapies. Since also correlating with histopathological findings, the analysis of serum hyaluronan might reduce the need for liver biopsy. Additionally, serum hyaluronan is a sensitive marker for the rejection of liver transplants.
Tumor marker
In certain tumors like prostate or breast cancer the serological hyaluronan level seems to correlate with malignancy. Serum hyaluronan might therefore be used to monitor disease progression as well as detect patients responding to chemotherapy in certain tumors. In bladder cancer the synthesis of hyaluronan is associated with tumor angiogenesis and metastasis. Thus, increased urinary levels of hyaluronan indicate the presence of bladder cancer regardless of tumor grade. The analysis of urine hyaluronan - in combination with the measurement of hyaluronidase - could therefore be used to detect bladder cancer as well as to monitor patients for residual
carcinoma after tumor resection.
Other applications
Hyaluronan concentrations have been also determined in various other sample types like perfusion and lavage fluids. Markedly increased hyaluronan levels were found in broncho-alveolar lavage fluids of patients with pulmonary inflammation like farmer’s lung, sarcoidosis or adult respiratory distress syndrome.
References
1. Laurent TC, Laurent UB, Fraser JR. Serum hyaluronan as a disease marker. Ann Med. 1996 Jun;28(3):241-53.
2. Lindqvist U et al. The diurnal variation of serum hyaluronan in health and disease.
Scand J Clin Lab Invest. 1988 Dec;48(8):765-70.
3. McHutchison JG, et al. Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its
relationship to liver histology. Consensus Interferon Study Group. J Gastroenterol Hepatol 2000; 15:945-51.
4. Stickel F, et al. Serum hyaluronate correlates with histological progression in alcoholic liver disease.
Eur J Gastroenterol Hepatol 2003; 15:945-50.
5. Lokeshwar VB, Block NL HA-HAase urine test. A sensitive and specific method for detecting bladder cancer and
evaluating its grade. Urol Clin North Am. 2000 Feb;27(1):53-61.

Hyaluronic Acid HA, ELISA, Livercirrhosis, Hyaluronate, Rheumatoid Arthritis, Hyaluronan, Osteoarthritis, Liverfibrosis, Cartilagemarker, Therapy efficiency, Fat metabolism, Fat tissue