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Collagen Synthesis in Tenocytes, Ligament Cells and Chondrocytes Exposed to a Combination of Glucosamine HCl and Chondroitin Sulfate
Journal of
Collagen Synthesis in Tenocytes, Ligament Cells and Chondrocytes Exposed to a Combination of Glucosamine HCl and Chondroitin Sulfate
Louis Lippiello 0 1
0 Laboratories Inc. , 2208 Lakeside Blvd, Edgewood, MD , USA. Tel:
1 Nutramax Laboratories Edgewood , MD 21040 , USA
Clinical testing of the nutraceuticals glucosamine (glcN) and chondroitin sulfate (CS) has shown efficacy in providing relief from symptoms in osteoarthritic patients. In vitro and in vivo studies support existence of a synergistic relationship upregulating synthetic activity in chondrocytes. A combination of glcN and CS may also be useful as adjunct therapy in sports-related injuries if similar upregulation of collagen synthesis is elicited in accessory ligament and tendon joint tissue. Collagen and noncollagenous protein (NCP) synthesis in cultures of bovine tenocytes, ligament cells and chondrocytes exposed to glcN þ CS were assayed by uptake of radiolabeled proline into collagenase-sensitive material. Assay of radiolabel in hydroxyproline (a specific marker for collagen synthesis) following HPLC isolation confirmed the specificity of the metabolic effect. Synthesis of total collagenasesensitive material was maximally upregulated at physiologically obtainable doses of glcN þ CS. Tissue response followed the sequence ligament cells (þ69%) > chondrocytes (þ56%) > tenocytes (þ22%). Labeled hydroxyproline increased by 132% in ligament cells, 27% in tenocytes and 49% in epitendon cells after a 48 h exposure to 5 mg ml 1 glcN þ 4 mg ml 1 CS. Low dose combinations of glcN and CS effectively stimulate in vitro collagen and NCP synthesis by ligament cells, tenocytes and chondrocytes. Hence, therapeutic use following accessory joint tissue trauma may help augment repair processes.
arthritis - metabolism alternative therapy
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The combination of glucosamine (glcN) and chondroitin
sulfate (CS) has been extensively tested for clinical efficacy
of symptomatic relief in patients with osteoarthritic (OA)
joints (1–4). Assessment of joint cartilage degeneration and
anti-inflammatory effects has also been examined in diverse
animal models of arthritis (5–8). In addition, in vitro and in
vivo studies support existence of a synergistic relationship of
these two agents associated with upregulation of matrix
proteoglycan synthesis and downregulation of metalloprotease
activity (1,9–11) suggesting a ‘chondroprotective’ effect. For
the most part, these studies have only examined responses of
articular chondrocytes but conceptually OA is considered a
disorder of the entire articulating joint including the ligament
and tendon accessory joint structures (12).
Ligaments and tendons are dense fibrous connective tissues
providing mechanical stability to joints during movement. The
cellular fibroblastic-like cells are surrounded by an organized
fibrous extracellular matrix composed primarily of type
I collagen, elastin, non-collagenous proteins (NCP), and
small amounts of keratan and CS. Aging-related alterations
or trauma to tendons and ligaments play a role in altering joint
dynamics and predispose the joint to early onset of
osteoarthritis (13,14). Tendon/ligament failure by traumatic rupture,
overuse and/or inflammatory processes is ranked as the 15th
most common musculoskeletal condition and 30–50% of all
sports injuries (15). Moreover, the annual incidence of acute
rupture of the anterior cruciate ligament has been estimated to
be one in 3000 in the American population, with 95 000 new
cases per year (16).
Current therapies for the treatment of ligament/tendon injuries
emphasize non-steroidal anti-inflammatory agents (NSAIDs)
to minimize inflammation and subsequent damage to tissue
integrity. However, caution has been recommended against
excessive use of some NSAIDs since these agents have an
inhibitory effect on proteoglycan synthesis and cell proliferation
(17) and in animal models do not provide any biochemical
benefit (18). A number of growth promoting factors including
platelet-derived growth factor, transforming growth factor beta
and basic fibroblast growth factor have demonstrated significant
stimulation of matrix synthesis in vitro but have not proved
successful in vivo (19). There is currently no efficacious therapy
for enhancing the rate and/or ability of these tissues to heal (17).
Nutraceutical supplements including creatine, ephedra, etc.,
have been associated with side effects and lack rigorous quality
assurance to warrant their use (20).
Clinical trials using nutraceutical preparations for healing
and minimizing inflammatory processes in dense connective
tissues have not been performed. The significant advantage
of such therapy for sports-related injuries is the possibility
of enhancing natural repair processes and/or minimizing
NSAIDs use.
The rationale for exploring whether the combination of
glcN þ CS has a beneficial effect on collagen synthesis in
ligaments and tendons is based on previous studies suggesting
that they act (...truncated)