What is osteoarthritis?
Osteoarthritis, also called degenerative joint disease, is caused by the breakdown of cartilage, which is the
connective tissue that cushions the ends of bones within the joint. It is characterized by pain, joint damage,
and limited motion. The disease generally occurs late in life, and most commonly affects the hands and large
weight-bearing joints. Although the disease can impact several joints, the knees are often affected. Age,
female gender, and obesity are risk factors for this condition.

Chondroitin glucosamine msm,  What does chondroitin do?
Glucosamine and chondroitin are natural substances found in and around the cells of cartilage. Researchers
believe these substances may help in the repair and maintenance of cartilage. In addition, researchers believe
that glucosamine inhibits inflammation and stimulates cartilage cell growth, while chondroitin provides cartilage
with strength and resilience. Currently, glucosamine and chondroitin are classified as dietary supplements.

Chondroitin sulfate is considered as a symptomatic slow-acting drug, i.e. a compound that has a slow onset
of action and improve osteoarthritis symptoms after a couple of weeks. Chondroitin sulfate exhibits a wide
range of biological activities and from a pharmacological point of view it produces a slow but gradual decrease
of the clinical symptoms of osteoarthritis and these benefits last for a long period after the end of treatment.
Many literature data show that chondroitin sulfate could have an anti-inflammatory activity and a
chondroprotective action by modifying the structure of cartilage. These properties are also related to the oral
adsorption of this molecule as high-molecular mass compounds having clusters of sulfate groups and high
charge density capable of exert their chondroprotective activity in vivo. However, please, note that all the
conclusive studies with chondroitin sulfate resulted from the use of experimental dosage designs, which may
different from commercially available supplements. [3,4] The oral absorption for an experimental chondroitin
sulfate formulation is 70%. [2]

How does chondroitin benefit osteoarthritis?
Chondroitin sulfates play a role in articular and bone metabolism by controlling cartilaginous matrix integrity
and bone mineralization. Chondroitin sulfates are synthesized in chondrocytes and in bone cells. Binding to
the core protein through N- and O-linkages leads to aggregates of monomers with high molecular weights.  
The proteoglycan aggregate exhibits viscoelastic and hydration properties and an ability to interact with the
surrounding tissue through electric charges leading to protection of the cartilaginous tissues.  Chondroitin
sulfates inhibit the activity of extracellular proteases for the connective tissues. In addition to their
anti-inflammatory effects, chondroitin sulfates in vitro stimulate proteoglycan production by chondrocytes; they
also inhibit cartilage cytokine production and induce apoptosis of articular chondrocytes. [14, 15]

Chondroitin sulfates increase the intrinsic viscosity of the synovial liquid. In vivo in experimental arthritis, the
number and severity of articular symptoms decreases after chondroitin sulfates administration. In bones,
chondroitin sulfates accelerate the mineralization process and bone repair. However, they break down easily
via enzymatic degradation ( metalloproteinases and lysosomal enzymes). [14]

What are the side effects of chondroitin?
Glucosamine and chondroitin sulphate are naturally occurring substances. Both substances can be taken by
mouth and have no known significant toxicity nor
side effects. Glucosamine and chondroitin sulphate have
been examined in laboratory and animal experiments, and in several clinical studies, which have shown some
effect on the symptoms of early or moderate arthritis. The long-term effect has not been evaluated sufficiently
and studies of the relation between dose and effect are lacking for both compounds. [5,6]

What are other health benefits of chondroitin sulfate?
Chondroitin sulphate has been found to be a major component for proteoglycans. Proteoglycans are
glycoproteins in the extracellular matrix. Among proteoglycans, the most abundant type is the hyalectan or
lectican family. Proteoglycans are formed by two main components; a protein and a sugar chain, which that is
termed glycosaminoglycan. These glycosaminoglycans are polymers of two simple sugars. The hyalectan
family has glycosaminoglycans of the chondroitin sulphate type, and they are termed
proteoglycans-chondroitin sulphate.

Chondroitin benefits - neural support
Proteoglycans-chondroitin sulphates are linked to the hyaluronic acid and other molecules of the extracellular
matrix in order to form a three-dimensional network. This network has several important roles in the
maintenance of the homeostasis of the central nervous system. [8-12]

Carulli D and co-workers from Cambridge University considered the possible benefits of chondroitin sulfate on
nerve cell regeneration. As described before, proteoglycans are of two main types, chondroitin sulfate and
heparin sulfate. The chondroitin sulfate acts mainly as barrier-forming molecules, whereas the heparin sulfate
stabilise the interactions of receptors and ligands. During development chondroitin sulfates pattern cell
migration, axon growth pathways and axon terminations. Later in development and in adulthood chondroitin
sulfates associate with some classes of neuron and control plasticity. After damage to the nervous system,
chondroitin sulfates are the major axon growth inhibitory component of the glial scar tissue that blocks
successful regeneration.

Chondroitin sulfates have a variety of roles in the nervous system, including binding to molecules and blocking
their action, presenting molecules to cells and axons, localising active molecules to particular sites and
presenting growth factors to their receptors. [1, 13]

Chondroitin benefits - anti-cancer?
Some researchers are interested in chondroitin's role in tumor cell invasion and metastasis. [14] Tumor cell
invasion and metastasis is highly dependent on dynamic changes in the adhesion and migration of
transformed and malignant cells. As with normal cell adhesion, the adhesion of tumor cells influences their
cytoskeletal organization, activation of signal transduction pathways within the cell, and nuclear events leading
to changes in mRNA transcription and protein synthesis. Furthermore, as tumor cells invade the circulation,
they adhere to activated endothelial cells at sites within the vasculature during arrest and extravasation.
Studies in the area of tumor cell adhesion and migration have demonstrated that the recognition of
extracellular matrix ligands, or adhesion promoting ligands expressed on neighboring cells (i.e.
counter-receptors), involves complex molecular recognition mechanisms. The complexity arises, in part, from
the multiple recognition sites that are present within adhesion promoting ligands. Some of these structures
within ECM components act by binding integrins, whereas others bind additional receptors such as cell surface
proteoglycans. In this sense, adhesion promoting ligands may be considered as informational arrays, that
function to modulate cell phenotype by engaging specific combinations of adhesion receptors on the cell
surface. Thus, cell surface chondroitin sulfate proteoglycans may play in modulating tumor cell adhesion,
migration and invasion.

2011
Epidemiologic studies have reported inverse associations of non-steroidal anti-inflammatory drug (NSAID) use
and lung cancer risk. Brasky TM et al at The Fred Hutchinson Cancer Research Center, Seattle, found that
ever use of glucosamine and chondroitin, which have anti-inflammatory properties, were inversely associated
with lung cancer risk. They run a survey and further proved the observation. Their results for glucosamine use
are similar to the prior human studies of NSAID use and lung cancer, both in magnitude and the limitation of
the association to adenocarcinoma. Unlike NSAIDs, glucosamine has no known adverse effects or serious side
effects. [Cancer Causes Control. 2011 Sep;22(9):1333-42.]

However, Brasky TM et al at Fred Hutchinson Cancer Research Center did not found any benefit of
chondroitin on prostate cancer from a survey of 35,239 male. [Nutr Cancer. 2011 May;63(4):573-82]

What is a dietary supplement?
A dietary supplement is a product (other than tobacco) intended to supplement the diet, which bears or
contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb, or other
botanical; is intended for ingestion in the form of a capsule, powder, softgel, or gelcap; and is not represented
as a conventional food or as a sole item of a meal or the diet (as defined by the U.S. Dietary Supplement
Health and Education Act, Oct. 25, 1994).

What is celecoxib?
Celecoxib (brand name Celebrex) is a new type of nonsteroidal anti-inflammatory drug (NSAID), called a
COX-2 inhibitor. Like traditional NSAIDS, celecoxib blocks the COX-2 enzyme in the body that stimulates
inflammation. Unlike traditional NSAIDS, however, celecoxib does not block the action of COX-1 enzyme, which
is known to protect the stomach lining. As a result, celecoxib reduces joint pain and inflammation with reduced
side effect of gastrointestinal ulceration and bleeding. However, (FDA Alert: 4/7/2005):Celebrex has been
associated with an increased risk of serious cardiovascular (CV) side effects in a long-term placebo controlled
trial. Thus, natural remedy with limited side effects may be still a choice for patients, users must discuss with
their doctor before taking any supplement.










































THIS ARTICLE IS FOR YOUR REFERENCE ONLY. IF YOU HAVE ANY QUESTION, PLEASE, CONSULT WITH YOUR DOCTOR IMMEDIATELY. MORE
RESEARCH STUDIES ARE NEEDED TO CONFIRM CHONDROITIN SULFATE BENEFITS ON OSTEOARTHRITIS AND OTHER CONDITIONS. ALL
RIGHTS RESERVED @2011. DO NOT COPY NOR TRANSFER THIS ARTICLE TO OTHER WEBSITES OR OTHER PUBLICATIONS WITHOUT
PERMISSION.

REFERENCE [1] Carulli D et al, Chondroitin sulfate proteoglycans in neural development and regeneration. Curr Opin Neurobiol. 2005
Apr;15(2):252. [2] Owens S Recent advances in glucosamine and chondroitin supplementation. J Knee Surg. 2004 Oct;17(4):185-93. [3] Volpi N
The pathobiology of osteoarthritis and the rationale for using the chondroitin sulfate for its treatment. Curr Drug Targets Immune Endocr Metabol
Disord. Jun;4(2):119-27.2004. [4] Reginster JY et al, Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in
the treatment of osteoarthritis. Curr Opin Rheumatol. 2003 Sep;15(5):651-5. [5] Angermann P Glucosamine and chondroitin sulfate in the treatment
of arthritis Ugeskr Laeger. 2003 Jan 27;165(5):451-4. [6] Bijlsma JW Glucosamine and chondroitin sulfate as a possible treatment for osteoarthritis
Ned Tijdschr Geneeskd. 2002 Sep 28;146(39):1819-23. [7] Brief AA et al, Use of glucosamine and chondroitin sulfate in the management of
osteoarthritis. J Am Acad Orthop Surg. 2001 Mar-Apr;9(2):71-8. [8] Crespo-Santiago D et al, The extracellular matrix of the central nervous system:
chondroitin sulphate type proteoglycans and neural repair Rev Neurol. 2004 May 1-15;38(9):843-51. [9]Grumet M et al, Functions of brain
chondroitin sulfate proteoglycans during developments: interactions with adhesion molecules. Perspect Dev Neurobiol. 1996;3(4):319-30. [10]
Margolis RU et al, Chondroitin sulfate proteoglycans as mediators of axon growth and pathfinding. Cell Tissue Res. 1997 Nov;290(2):343-8. [11]
Oohira A et al, Molecular interactions of neural chondroitin sulfate proteoglycans in the brain development. Arch Biochem Biophys. 2000 Feb
1;374(1):24-34. [12] Rauch U et al, Neurocan: a brain chondroitin sulfate proteoglycan. Cell Mol Life Sci. 2001 Nov;58(12-13):1842-56. [13] Zhuo L
et al, A physiological function of serum proteoglycan bikunin: the chondroitin sulfate moiety plays a central role. Glycoconj J. 2002
May-Jun;19(4-5):241-7. [14] Bali JP et al, Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system.
Semin Arthritis Rheum. 2001 Aug;31(1):58-68. [15] Kelly GS The role of glucosamine sulfate and chondroitin sulfates in the treatment of
degenerative joint disease. Altern Med Rev. 1998 Feb;3(1):27-39. [16] Iida J et al, Cell surface chondroitin sulfate proteoglycans in tumor cell
adhesion, motility and invasion. Semin Cancer Biol. 1996 Jun;7(3):155-62.
Chondroitin side effects, chondroitin benefits
Chondroitin glucosamine msm,  What does chondroitin do?
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