Collagen Synthesis in Tenocytes, Ligament Cells and Chondrocytes Exposed to a Combination of Glucosamine HCl and Chondroitin Sulfate

Evidence-Based Complementary and Alternative Medicine, Sep 2018

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 non-collagenous protein (NCP) synthesis in cultures of bovine tenocytes, ligament cells and chondrocytes exposed to glcN + 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 collagenase-sensitive material was maximally upregulated at physiologically obtainable doses of glcN + CS. Tissue response followed the sequence ligament cells (+69%) > chondrocytes (+56%) > tenocytes (+22%). Labeled hydroxyproline increased by 132% in ligament cells, 27% in tenocytes and 49% in epitendon cells after a 48 h exposure to 5 μg ml−1 glcN + 4 μg 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.

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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 - 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)


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Louis Lippiello. Collagen Synthesis in Tenocytes, Ligament Cells and Chondrocytes Exposed to a Combination of Glucosamine HCl and Chondroitin Sulfate, Evidence-Based Complementary and Alternative Medicine, 4, DOI: 10.1093/ecam/nel081