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

      research-article
      Evidence-based Complementary and Alternative Medicine
      Oxford University Press
      arthritis, metabolism alternative therapy

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          Abstract

          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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          Most cited references45

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          Treatment of anterior cruciate ligament injuries, part I.

          Anterior cruciate ligament injuries are common among athletes. Although the true natural history remains unclear, anterior cruciate ligament injuries are functionally disabling; they predispose the knee to subsequent injuries and the early onset of osteoarthritis. This article, the first in a 2-part series, was initiated with the use of the PubMed database and a comprehensive search of articles that appeared between January 1994 to the present, using the keywords anterior cruciate ligament. A total of 3810 citations were identified and reviewed to determine the current state of knowledge about the treatment of these injuries. Articles pertaining to the biomechanical behavior of the anterior cruciate ligament, the prevalence of anterior cruciate ligament injury, the natural history of the anterior cruciate ligament-deficient knee, injuries associated with anterior cruciate ligament disruption, risk factors for anterior cruciate ligament injury, indications for treatment of anterior cruciate ligament injuries, and nonoperative and operative treatments were obtained, reviewed, and served as the basis for part I. Part II, to be presented in another issue of this journal, includes technical aspects of anterior cruciate ligament surgery, bone tunnel widening, graft healing, rehabilitation after reconstruction, and the effect of sex, age, and activity level on the outcome of surgery. Our approach was to build on prior reviews and to provide an overview of the literature for each of the before-mentioned areas of study by summarizing the highest level of scientific evidence available. For the areas that required a descriptive approach to research, we focused on the prospective studies that were available; for the areas that required an experimental approach, we focused on the prospective, randomized controlled trials and, when necessary, the highest level of evidence available. We were surprised to learn that considerable advances have been made during the past decade regarding the treatment of this devastating injury.
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            Biological Basis for the Use of Botanicals in Osteoarthritis and Rheumatoid Arthritis: A Review

            Osteoarthritis (OA) of the knee and hip is a debilitating disease affecting more women than men and the risk of developing OA increases precipitously with aging. Rheumatoid arthritis (RA), the most common form of inflammatory joint diseases, is a disease of unknown etiology and affects ∼1% of the population worldwide, and unlike OA, generally involves many joints because of the systemic nature of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first drugs of choice for the symptomatic treatment of both OA and RA. Because of the risks associated with the use of NSAIDs and other limitations, the use of alternative therapies, such as acupuncture and medicinal herbs, is on the rise and according to reports ∼60–90% of dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine (CAM). This paper reviews the efficacy of some of the common herbs that have a history of human use and their anti-inflammatory or antiarthritic properties have been evaluated in animal models of inflammatory arthritis, in studies employing well defined and widely accepted in vitro models that use human chondrocytes/cartilage explants or in clinical trials. Available data suggests that the extracts of most of these herbs or compounds derived from them may provide a safe and effective adjunctive therapeutic approach for the treatment of OA and RA. This, in turn, argues for trials to establish efficacy and optimum dosage of these compounds for treating human inflammatory and degenerative joint diseases.
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              Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy.

              Glucosamine is widely used to relieve symptoms from osteoarthritis. Its safety and effects on glucose metabolism are critically evaluated in this review. The LD50 of oral glucosamine in animals is approximately 8000 mg/kg with no adverse effects at 2700 mg/kg for 12 months. Because altered glucose metabolism can be associated with parenteral administration of large doses of glucosamine in animals and with high concentrations in in vitro studies, we critically evaluated the clinical importance of these effects. Oral administration of large doses of glucosamine in animals has no documented effects on glucose metabolism. In vitro studies demonstrating effects of glucosamine on glucose metabolism have used concentrations that are 100-200 times higher than tissue levels expected with oral glucosamine administration in humans. We reviewed clinical trial data for 3063 human subjects. Fasting plasma glucose values decreased slightly for subjects after oral glucosamine for approximately 66 weeks. There were no adverse effects of oral glucosamine administration on blood, urine or fecal parameters. Side effects were significantly less common with glucosamine than placebo or non-steroidal anti-inflammatory drugs (NSAID). In contrast to NSAID, no serious or fatal side effects have been reported for glucosamine. Our critical evaluation indicates that glucosamine is safe under current conditions of use and does not affect glucose metabolism.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                eCAM
                Evidence-based Complementary and Alternative Medicine
                Evidence-based Complementary and Alternative Medicine
                Oxford University Press
                1741-427X
                1741-4288
                June 2007
                1 December 2006
                : 4
                : 2
                : 219-224
                Affiliations
                Nutramax Laboratories Edgewood MD 21040, USA
                Author notes
                For reprints and all correspondence: Dr Louis Lippiello, Nutramax Laboratories Inc., 2208 Lakeside Blvd, Edgewood, MD, USA. Tel: +1-410-420-0743; Fax: +1-410-532-4784; E-mail: l.lippiello@ 123456att.net
                Article
                10.1093/ecam/nel081
                1876619
                17549239
                d05809e8-bdaf-4190-af7a-2170c3d5380c
                © 2006 The Author(s).

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 February 2006
                : 25 September 2006
                Categories
                Original Articles - Basic Sciences

                Complementary & Alternative medicine
                arthritis,metabolism alternative therapy
                Complementary & Alternative medicine
                arthritis, metabolism alternative therapy

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