EXPIRATION DATE: 1/23/2017
Tendon & Ligament provides vital support for the 4 physical attributes all elite athletes require for success. While most joint products maintain the state of the joint. Tendon & Ligament helps build, strengthen, and support joint components to sustain an athlete's functional strength. It goes beyond the joints to further support overall healthy skin and connective tissue.*
Improve flexion and compression at vital pivot points!*
What's more, connective tissues and joint structures such as muscle, bone, and cartilage require certain nutrients to assist in building and supporting overall health.* Tendon & Ligament performance provides these nutrients in 3 ways:
Date: 2012 Active Ingredients (per serving):
Collagen Type I (11g)
Collagen Type II (40 mg)
Hyaluronic acid (20 mg)
Maintaining the structures of bones, ligaments, tendons, and joints is essential in the physical performance of athletes as is the upholding of nutrients required to support these structures.
Collagen is a term for proteins forming a characteristic triple helix of three polypeptide chains. All these structures are formed in the extracellular matrix. However their size, function and tissue distribution varies considerably. So far up to 28 types of collagen types have been identified to date in the body (Gelse 2003; Shoulders 2009). Collagen is the main structural protein found in the human body (Gelse 2003; Kadler 1996) and a total of about 25-35% of the total protein composition in the human body is comprised of collagen (Gelse 2003; Yalovac 2007). Collagen is especially found in bone, muscle, tendons, ligaments, cartilage, skin and other connective tissues (Gelse 2003).
The different collagen types have complex and diverse structure and functionality due to additional structural domains and folding (Gelse 2003; Shoulders 2009). About 90% of total collagen comes from fibril-containing collagens. Collagen Type I and V primarily contribute to the structural make-up of bone. Collagen Type II and XI primarily contribute to the articular cartilage matrix. The tensile strength and torsional stability renders these tissues with stability and integrity (Birk 1988, Gelse 2003, Mayne 1989 von der Mark 1999). Other collagens might be more flexible such as the collagen found in the cartilage of our ears (Gelse 2003), or interwoven with other collagen to create various sorts of networks (Gelse 2003, von der Mark 1984).
Although there are many structural variations among the identified collagens they all have one characteristic among them: they all have a right-handed triple helix composed of three identical chains (such as in Type II collagen) or they have two or more different chains (such as collagen Type I) (Gelse 2003; Kadler 1996; Kühn 1986, Piez 1984). Each of the 3 a-chains is composed of 18 amino acids and rotate in a left-handed manner. The three chains are then super-coiled around each other to form the right-handed triple helix (Fraser 1979, Gelse 2003, Hofmann 1978,).
The classical fibril-forming collagens include types I, II, III, V, and XI. Fibrillar collagens are characterized by their ability to pack into tightly oriented aggregates with a staggered pattern (Gelse 2003; Shoulders 2009). It has been said that healthy fibrillar collagen is stronger than steel (REF). For the sake of space and interest only Collagen Type I and II will be discussed below.
Various collagen types (IX, XII, XIV, XVI, XIX, and XX) belong to the Fibril-Associated-Collagens with Interrupted Triple helices (FACIT) (Gelse 2003). These structures have collagenous domains which are interrupted by short non-helical domains and they are usually associated with the surfaces of various fibrils. For example, Collagen Type IX is associated with Type II fibrils in an anti-parallel direction (Gelse 2003, von der Mark 1999, Wu 1995) in cartilage and the vitreous body of the eye (Gelse 2003, von der Mark 1999). This allows for the interaction of proteoglycans and other matrix components such as chondroitin sulfate (Gelse 2003, Mayne 1989, van der Rest 1988, Yada 1990).
There are many more collagen types found in the body. These include network-forming collagens, anchoring fibrils, transmembrane collagens, basement membrane collagens, etc. (Gelse 2003). They all maintain the structural integrity of tissue and organs in the human body.
Collagens also are also involved in cellular microenvironment. Due to their binding and network-forming/anchoring capacity, they are involved in cell signaling of adhesion, differentiation, growth, cellular re-activities as well as contribute to the formation and promotion of tissue repair and regeneration (Frenkel 1997, Gelse 2003; Schuppan 1998, Wakitani 1989). They also bind to growth factors and cytokines and thus might play a role in organ development (Gelse 2003, Hay 1981, Yamaguchi 1990).
PHYSIOLOGICAL ROLES OF COLLAGEN AND HYALURONIC ACID
Type I Collagen
Collagen Type I is one of the most important stress-carrying protein structures in the humans (Fratzl 1997). This collagen type is the most common and abundant form and forms >90% of the organic mass of bone. It is the major type of collagen in tendons, ligaments, skin, cornea of the eye, interstitial connective tissues, and arterial walls. It also makes up scar tissue and can be found in teeth (Di Lullo 2002; Gelse 2003).
The triple helix usually comprises of two identical a1-chains and one slightly different a2-chain and is usually incorporated together with either collagen Type III (as in the skin) or collagen type V (as in bone, tendon, and cornea) (Fleischmajer1990; Gelse 2003; Kadler 1996; Niyibizi 1989; Shoulders 2009). This protein has an atypical amino acid composition because it is relatively high in the amino acid hydroxyproline. The collagen molecule (also known as tropocollagen) is a subunit of the larger aggregates such as fibrils. Each tropocollagen has a left-handed rotation helix and three of these are twisted together to form the right-handed triple helix we all know with a length of about 300nm and about 1.5 nm in diameter (Kadler 1996; Makaareva 2007). This triple helix is stabilized by numerous hydrogen bonds and then further twist together with other triple-helices to form a microfibril (Perumal 2008).
A distinct feature of each tropocollagen is the regular amino acid arrangement of Glycine-Proline-XXX or Glycine-XXX-Hydroxyproline, where XXX is any other amino acid. The high Gly content allows the three helices to tightly wind around each other and facilitate hydrogen bonds as well as molecular cross-links between the molecules. Due to the high concentration of proline and hydroxyproline the geometrical constraint shows a tendency of the tropocollagen to have a left-handed rotation and the subunits to self-assemble. In the triple helix, glycine is in the interior towards the middle and the Pro and Hydroxy-Pro side chains are facing the outside (Yalovac 2007).
Collagen Type I provides tensile stiffness especially in tendons and fascia. In bone it defines the biochemical properties regarding load bearing, tensil strength, and stiffness especially after mineralization. Here the collagen triple-helices are arranged in a parallel and staggered pattern. The small gap at each end of the tropocollagen subunits most likely serves as a nucleation site for depositing calcium minerals (Ross 2011).
Collagen acts to transmit forces and dissipate energy and one of the important mechanical characteristics of collagenous tissue such as tendons and ligaments is its ability to store and transmit energy elastically during mechanical deformation (Pins 1997). Tendons are the energy transfer bridge between contracting muscles to bone, with the result of movement of the extremity. During normal gait, the body decelerates as the foot lands on the ground, causing kinetic energy to be stored in the stretched muscles and tendons. Elastic recoil in the tendons converts most of the energy into kinetic energy as the foot leaves the ground and the circle is complete (Freeman 2005, Silver 2001).
Ligaments absorb energy during the movement in order to protect joints from damage. For example the anterior cruciate ligament (ACL) absorbs energy during movement that could lead to anterior translation of the tibia, and thus prevents knee damage.
As the collagenous tissues are cross-linked and mineralized the energy storage ability of the tissue can be altered (Freeman 2005, Silver 2000).
Type II Collagen
Hyaline cartilage (as seen in joints) contains around 50-80% predominately Collagen Type II fibrils (Gelse 2003; Shoulders 2009). Type II Collagen can also be found in the vitreous body, corneal epithelium, nucleus pulposus of intervertebral discs, and embryonic epithelial-mesenchymal transitions (Gelse 2003, von der Mark 1999). The triple helix comprised of three identical chains to form a helix that is similar in size and biomechanical properties as Collagen Type I (Bruckner 1994, Gelse 2003). Cartilage also contains collagen types IX and XI to limit the size potential of collagen type II fibrils diameters (Gelse 2003, Mendler 1989, van der Rest 1991). Type II collagen contains a higher concentration of hydroxylysine as well as glycosyl and galactosyl residues. These mediate the interaction to proteoglycans, another important component of highly hydrated hyaline cartilage (Gelse 2003; Mayne 1989).
The purpose of the cartilage-bone interface in the joint such as the knee, is to maintain structural integrity during physical movements such as walking, kneeling, running, pivoting, jumping, etc. (Hoemann 2012). At those moments tensile, compressive and shear forces are transmitted from the articular cartilage, which is more viscoelastic, to the much stiffer mineralized end of the bone. Articular cartilage is attached to the subchondral bone through a 20-250 mm thick layer of calcified cartilage and the type II collagen fibers become structurally cemented to type I collagen osteoid deposited by osteoblasts (cells responsible for bone formation).
Hyaluronic acid (HA) is the largest non-sulfated glycosaminoglycan (GAG; a polymer of D-glucuronic acid + N-acetylglucosamine) which is primarily found in connective, epithelial, neural tissue, and synovial fluid (Armstrong 1997; Hong 2004). It is one of the main components of extracellular matrix as well as synovial fluid where it increases viscosity and is together with lubricin one of the fluids lubricating component. It is an important component of joint cartilage, where it interacts with chondrocytes. It is a negatively charged protein and forms aggregates that bind water and are responsible for the resiliance of cartilage (Toole 2000).
Cell receptors for hyaluronic acid have also been identified and so far fall into three categories: CD44, Receptor for HA-mediated motility (RHAMM) and intracellular adhesion molecule-1 (ICAM-1). CD44 and ICAM-1 are already known as cell adhesion molecules with other recognized ligands before their HA binding was discovered. CD44 is widely distributed throughout the body, and the formal demonstration of HA-CD44 binding was proposed by Aruffo et al. in 1990. To date, it is recognized as the main cell surface receptor for HA. CD44 mediates cell interaction with HA and the binding of the two functions as an important part in various physiologic events, such as cell aggregation, migration, proliferation and activation; cell-cell and cell-substrate adhesion; endocytosis of HA.
ICAM-1 is known mainly as a metabolic cell surface receptor for HA, and this protein may be responsible mainly for the clearance of HA from lymph and blood plasma, which accounts for perhaps most of its whole-body of this receptor, thus, triggers a highly coordinated cascade of events that includes the formation of an endocytotic its fusion with primary enzymatic digestion to active transmembrane transport of these sugars to cell sap, Like its name, ICAM-1 may also serve as a cell adhesion molecule, and the binding of HA to ICAM-1 may contribute to the control of ICAM-1-mediated inflammatory activation.
The major difference in biological activities is attributed to its variable molecular weight. There are clear molecular weight cut-offs for HA's lubricating properties, cell-signaling, and efficacy for joint support. Molecular weight of less than 500 kD seems to be the magic cut-off target number (Camenisch 2000). Very low MW HA fragments either do not bind to specific cell membrane receptors that recognize native HA or they transduce different signals to cells (Bucci 2004). The molecular weight between 700,000 and 1,000,000 is used in Tendon & Ligament. The majority of in vitro and animal research showed stimulated synthesis of HA from human osteoarthritic synovial fibroblasts and anabolic reactions in extracellular matrix components (proteoglycan synthesis, enhanced chondroitin proliferation and synthesis, improve bone mineralization, decrease cartilage degradation, antioxidant activity, regulatory function, etc.) (Bucci 2004).
CLINICAL SIGNIFICANCE OF TENDON & LIGAMENT
STRONGER AND MORE SOLID FOUNDATION
Clinical studies investigating the effects of hydrolyzed collagen have been done for a few decades (Bello 2006). Hydrolyzed collagen is a source of bioavailable peptide fragments and a rich source of the important amino acids for tendons, ligaments and bones, i.e. glycine, proline, hydroxyproline, lysine, and hydroxylysine. Absorption studies in both animals and humans (at amounts found in Tendon & Ligament) have shown that hydrolyzed collagen is readily absorbed throughout the body and supplies collagen-containing tissues with these building blocks (Oesser 1999).
Absorption studies of hyaluronic acid (HA) have also been done in animals and shows that HA is preferably taken up in joints and skin (Balogh 2008; Schauss 2004) as well as liver, spleen, bone marrow and lymph nodes (Fraser 1983; Fraser 1989; Westerberg 1995. The human body metabolizes large quantities of HA daily as well as have a large capacities to remove HA from the bloodstream (Fraser 1984; Fraser 1986; Fraser 1989; Laurent 1992; Lebel 1994; Lindqvist 2000).
With the combination of Collagen Type I, HA and Collagen Type II a solid foundation is laid that provides the necessary building blocks to sustain bone, tendons, ligaments, and cartilage. Thus all the building blocks are there to maintain and build a stronger and more solid foundation for athletic performances.
STRONGER CONNECTIVE TISSUE AND INCREASED ELASTICITY
Fernandez and Perez (1998) investigated the effects of 10g of hydrolyzed collagen on shoulder and knee joints in healthy male competitive mountain bikers during a six-month trial. Biometric ultrasounds of the cartilages showed statistically significant increases in cartilage thickness, whereas the controls showed no or decreases cartilage thickness. In another study 84 German athletes with painful knee, hip, and shoulder joints were examined for 12 weeks after ingesting 10g/d hydrolyzed collagen. The results showed decrease in knee, hip, and shoulder pain at rest and during test exercise (Flechsenhar 2005). Another research group investigated the effects of 10g of hydrolyzed collagen in healthy and physically active at club levels complaining of joint pain or discomfort (Clark 2008). After 24 weeks of treatment this randomized, placebo-controlled, double-blind study showed significant improvement in joint pain using a Visual Analogue Scale. In vitro tissue culture studies have shown that in the presence of hydrolyzed collagen joint chondrocytes were able to stimulate type II collagen biosynthesis over the 11 day testing period. This suggests that hydrolyzed collagen might have a stimulatory effect on type II collagen biosynthesis of chondrocytes (Oesser 2003).
Undenatured Type II Collagen, called UC-II from Inter Health N.I., is a patented ingredient derived from chicken sternum cartilage. During manufacturing native epitopes of collagen type II are preserved and remain immune-reactive as it passes through the gut to the small intestine where the Peyer's Patches absorb them (Bagchi 2002). Once in the lymphoid tissue UC-II works together with the immune system to modulate the breakdown of joint cartilage and prevent degradation of type II collagen in the joints as well as support rebuilding of cartilage. Collagen specific, regulatory T-cells migrate to the joint areas and modulate the ongoing local inflammatory responses. Collagenase secretion by macrophages is slowed down and the production of inflammatory cytokines as well. As inflammation reactions subside, the imbalance of cartilage turnover appears to shift in favor of normal cartilage rebuilding (Bagchi 2002; Hu 2003; Nagler-Anderson 1986; Park 2009; Prakken 2004).
Many studies have been performed in animals (Thompson 1985, Zhang 1990), especially horses and dogs with arthritis (D'Altilio 2007, Deparle 2005; Gupta 2009). All studies show vast improvements in clinical symptoms of arthritis. In a randomized, double-blind, clinical study using the same amount of UC-II as found in Tendon & Ligament 52 subjects with knee osteoarthritis where supplemented for 90 days and compared to a group supplemented with 1500 mg glucosamine + 1200 mg chondroitin (GC group: the standard supplementation). Total WOMAC scores declined by 33% as compared to 14% in the GC group and was 2x more effective in promoting joint comfort, flexibility and mobility compared to baseline. UC-II was 70% more effective at 30 days than GC (Crowley 2009).
Other studies have also investigated the effects of UC-II in human subjects with arthritis and found that undenatured type II collagen improved arthritis symptoms significantly (Barnett 1998; Trentham 1993; Wei 2009, Zhang 2008)
SECURE JOINT STRUCTURE
With improvement in the articular components using collagen type I (Bello 2006; Clark 2008; Fernandez-Perez 1998; Flechsenhar 2005; Oesser 1999), undenatured Collagen Type II (Bagchi 2002, Barnett 1998; Crowley 2009; Hu 2003; Nagler-Anderson 1986; Park 2009; Prakken 2004; Trentham 1993; Wei 2009; Zhang 2008), and hyaluronic acid (Balogh 2008; Fraser 1984; Fraser 1986; Fraser 1989; Laurent 1992; Lebel 1994; Lindqvist 2000; Schauss 2004), the joints become a healthier place. Healthier joints mean healthier overall function. With Tendon & Ligament, the structural components of the joints such as the tendons, ligaments and bone receive the proper nourishment and building blocks to regenerate and maybe even repair and thus secure the joint structure better and more efficient.
Tendon & Ligament provides all the building blocks for a stronger and more solid foundation, stronger connective tissue, increased elasticity and thus secure joint structure for athletes. It creates a healthier environment within and around joints by targeting bones, ligaments, tendons, cartilage and the synovial fluid.
1. Armstrong DC, Johns MR. Culture conditions affect the molecular weight properties of hyaluronic acid produced by Streptococcus zooepidemicus. Appl Environ Microbiol 1997; 63(7):2759-2764.
2. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell 1990; 61(7):1303-1313.
3. Bagchi D, Misner B, Bagchi M, Kothari SC, Downs BW, Fafard RD, Preuss HG. Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration. Int J Clin Pharmacol Res 2002; 22(3-4):101-110.
4. Balogh L, Polyak A, Mathe D, Kiraly R, Thuroczy J, Terez M, Janoki G, Ting Y, Bucci LR, Schauss AG. Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs. J Agric Food Chem 2008; 56(22):10582-10593.
5. Barnett ML, Kremer JM, St. Clair EW, Clegg DO, Furst D, Weisman M, Fletcher MJF, Chasan-Taber S, Finger E, Morales A, Le CH, Trentham DE. Treatment of rheumatoid arthritis with oral type II collagen. Arthritis Rheum 1998; 41(2):290-297.
6. Bello AE, Oesser S. Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature. Curr Med Res Opin 2006; 22:221-232.
7. Birk DE, Fitch JM, Babiarz JP, Linsenmayer TF. Collagen type I and type V are present in the same fibril in the avian corneal stroma. J Cell Biol 1988; 106:999-1008.
8. Bruckner P, van der Rest M, Structure and function of cartilage collagens. Microsc Res Tech 1994; 28:378-384.
9. Bucci LR, Turpin AA. Will the real hyaluronan please stand up? J Appl Nutr 2004; 54(1):10-33.
10. Camenisch TD, McDonald JA. Hyaluronan: is bigger better? Am J Respir Cell Mol Biol 2000; 23(4):431-433.
11. Clark KL, Sebastianelli W, Flechsenhar KR, Aukerman DF, Meza F, Millard PL, Deitch JR, Sherbondy PS, Albert A. 24-Week study on the use of a collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Opin 2008; 24:1485-1496.
12. Crowley DC, Lau FC, Sharma P, et al. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci. 2009; 6:312-321.
13. D'Altilio M, Peal A, Alvey M, Simms C, Curtsinger A, Gupta RC, Canerdy TD, Goad JT. Therapeutic efficacy and safety of undenatured type II Collagen singly or in combination with glucosamine and chondroitin in arthritic dogs. Toxicol Mechanism Methods 2007; 17:189-196.
14. Deparle LA, Gupta RC, Canerdy TD, Goad JT, D'Altilio, Bagchi M, Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dog. J Vet Pharmacol Therap 2005; 28:385-390.
15. Di Lullo GA, Sweeney SM, KörkköJ, Ala-Kokko L, San Antonio JD. Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, Type I Collagen. J Biol Chem 2002; 277 (6):4223-4231.
16. Fernandez JL, Perez OM. Effects if gelatine hydrolysates in the prevention of athletic injuries. Archivos de Medicina del Deporte 1998; 15:277-282.
17. Flechsenhar KR, Alf D. Results of a postmarketing surveillance study. Orthopaedische Praxis 2005; 41:486-494.
18. Fleischmajer R, MacDonald ED, Perlish JS, Burgeson RE, Fisher LW. Dermal collagen fibrils are hybrids of type I and type III collagen molecules. J Struct Biol 1990; 105:162-169.
19. Fraser JR, Appelgren LE, Laurent TC. Tissue uptake of circulating hyaluronic acid. A whole body autoradiographic study. Cell Tissue Res 1983; 233(2):285-293.
20. Fraser JR, Engstrom-Laurent A, Nyberg A, Laurent TC. Removal of hyaluronic acid from the circulation in rheumatoid disease and primary biliary cirrhosis. J Lab Clin Med 1986; 107(1):79-85.
21. Fraser JR, Laurent TC. Turnover and metabolism of hyaluronan. Ciba Found Symp 1989; 143:41-53; discussion 53-59, 281-285.
22. Fraser JR, Laurent TC, Engstrom-Laurent A, Laurent UG. Elimination of hyaluronic acid from the blood stream in the human. Clin Exp Pharmacol Physiol 1984; 11(1):17-25.
23. Fraser RD, MacRae TP, Suzuki E. Chain conformation in the collagen molecule. J Mol Biol 1979; 129:463-481.
24. Fratzl P, Klaus Misof K, Zizak I. Fibrillar structure and mechanical properties of collagen. J Struct Biol 1997; 122:119-122.
25. Freeman JW, Silver FH, Woods MD, Laurencin CT. The role of Type I collagen molecular structure in tendon elastic energy storage. Mater Res Soc Symp Proc 2005; 874:L1.6.1
26. Frenkel SR, Toolan B, Menche D, Pitman MI, Pachence JM. Chondrocyte transplantation using a collagen bilayer matrix for cartilage repair. J Bone Jt Surg 1997; 79-B:831-836.
27. Gelse K, Pöschl E, Aigner T. Collagens—structure, function, and biosynthesis. Adv Drug Deliv Rev 2003; 55:1531-1546.
28. Gupta RC, Canerdy TD, Skaggs P, Stocker A, Zyrkowski G, Burke R, Wegford K, Goad JT, Rohde K, Barnett D, DeWees W, Bagchi M, Bagchi D. Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses. J Vet Pharmacol Therap 2009; 32:577-584.
29. Hay ED. Extracellular matrix. J Cell Biol 1981; 91:205s-223s.
30. Hofmann H, Fietzek PP, Kuhn K. The role of polar and hydrophobic interactions for the molecular packing of type I collagen: a three-dimensional evaluation of the amino acid sequence. J Mol Biol 1978; 125:137-165.
31. Hong SS, Chen J, Zhang JG, Tao YC, Liu LY. Purification and structure identification of hyaluronic acid. Chin Chem Lett 2004; 15(7):811-812.
32. Hu Y, Zhao W, Qian X, Zhang L. Effects of oral administration of type II collagen on adjuvant arthritis in rats and its mechanisms. Chin Med J 2003; 116:284-287.
33. Kadler KE, Holmes DF, Trotter JA, Chapman JA. Collagen fibril formation. Biochem J 1996; 316:1-11.
34. Kühn K. The collagen family-variations in the molecular and supermolecular structure. Rheumatol 1986; 10:29-69.
35. Laurent TC, Fraser JR. Hyaluronan. FASEB J 1992; 6(7):2397-2404.
36. Lebel L, Gabrielsson J, Laurent TC, Gerdin B. Kinetics of circulating hyaluronan in humans. 4. Eur J Clin Invest 1994; 24(9):621-626.
37. Lindqvist U, Westerberg G, Bergstrom M, Torsteindottir I, Gustafson S, Sundin A, Loof L, Langstrom B. [11C]Hyaluronan uptake with positron emission tomography in liver disease. Eur J Clin Invest 2000; 30(7):600-607.
38. Makareeva E, Mertz EL, Kuznetsova NV, Sutter MB, DeRidder AM, Cabral WA, Barnes AM, McBride DJ, Marini JC, Leikin S. Structural Heterogeneity of Type I collagen triple helix and its role in osteogenesis imperfecta. J Biol Chem Chem 2008; 283(8):4787-4798.
39. Mayne R. Cartilage collagens—what is their function, and are they involved in articular disease? Arthritis Rheum 1989; 32-3:241-246.
40. Mendler M, Eich-Bender SG, Vaughan L, Winterhalter KH, Bruckner P. Cartilage contains mixed fibrils of collagen types II, IX and XI. J Cell Biol 1989; 108:191-197.
41. Nagler-Anderson C, Bobert LA, Robinson ME, Siskind GW, Thorbecke GJ. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen (orally induced immunologic unresponsiveness/autoimmunity). Proc Natl Acad Sci USA 1986; 83:7443-7446.
42. Niyibizi C, Eyre DR. Bone type V collagen: chain composition and location of a trypsin cleavage site. Connect Tissue Res 1989; 20:247-250.
43. Oesser S, Seifert J. Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen. Cell Tissue Res 2003; 311:393-399.
44. Park KS, Park MJ, Cho ML, et al. Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheumatoid arthritis. Mod Rheumatol 2009; 19:581-589.
45. Perumal S, Antipova O, Orgel JPR. Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis. PNAS 2008; 105(8):2824-2829.
46. Piez KA. 1984. Molecular and aggregate structure of the collagens, In: Extracellular Matrix Biology Pietz KA, Reddi H (Eds.). Elsevier, Amsterdam, pp. 1-39.
47. Pins GD, Christiansen DL, Patel R, Silver FH. Self-assembly of collagen fibers. Influence of fibrillar alignment and decorin on mechanical properties. Biophys J 1997; 73(4):2164-2172.
48. Prakken BJ, Samodal R, Le TD, Giannoni F, Yung GP, Scavulli J, Amox D, Roord S, de Kleer I, Bonnin D, et al. Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci USA 2004; 101(12):4228-4233.
49. Ross MH, Pawlina W. 2011. Histology, 6th Ed.
50. Schauss AG, Balogh L, Polyak A, Mathe D, Kiraly R, Janoki G. Absorption, distribution and excretion of 99mtechnetium labeled hyaluronan after single oral doses in rats and beagle dogs. FASEB J 2004; 18(4):A150-A151. [abstract 129.4]
51. Schuppan D, Schmid M, Somasundaram R, Ackermann R, Ruehl M, Nakamura T, Riecken EO. Collagens in the liver extracellular matrix bind hepatocyte growth factor. Gastroenterology 1998; 114:139-152.
52. Shoulders MD, Raines RT. Collagen Structure and Stability. Annu Rev Biochem 2009; 78:929-958.
53. Silver FH, Christiansen DL, Snowhill PB, Chen Y. Role of storage on changes in the mechanical properties of tendon and self-assembled collagen fibers. Connect Tissue Res 2000; 41(2):155-164.
54. Silver FH, Freeman JW, Horvath I, Landis WJ. Molecular basis for elastic energy storage in mineralized tendon. Biomacromol 2001; 2(3):750-756.
55. Thompson HSG, Staines NA. Gastric administration of type II collagen delays the onset and severity of collagen-induced arthritis in rats. Clin Exp Immunol 1985; 64:581-586.
56. Toole BP. Hyaluronan is not just a goo! J Clin Invest 2000; 106(3):335-336.
57. Trentham DE. Evidence that type II collagen feeding can induce a durable therapeutic response in some patients with arthritis. Ann NY Acad Sci 1996; 306-314.
58. Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HL. Effects of oral administration of type II collagen on rheumatoid arthritis. Science 1993; 261(5129):1727-1730.
59. Van der Rest M, GarroneA R. Collagen family of proteins. FASEB J 1991; 5:2814-2823.
60. Van der Rest M, Mayne R. Type IX collagen proteoglycan from cartilage is covalently cross-linked to type II collagen. J Biol Chem 1988; 263:1615-1618.
61. Von der Mark H, Aumailley M, Wick G, Fleischmajer R, R. Timpl R. Immunochemistry, genuine size and tissue localization of collagen VI. Eur J Biochem 1984; 142:493-502.
62. Von der Mark K. 1999. Structure, biosynthesis and gene regulation of collagens in cartilage and bone. In: Dynamics of Bone and Cartilage Metabolism. Academic Press, Orlando, pp. 3-29.
63. Wakitani S, Kimura T, Hirooka A, Ochi T, Yoneda M, Yasui N, Owaki H, Ono K. Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. J Bone Jt Surg 1989; 71-B:74-80.
64. Wei W, Zhang L-L, Xu J-H, Xiao F, Bao C-D, Ni L-Q, Li X-F, Wu Y-Q, Sun L-Y, Zhang R-H, Sun B-L, Xu S-Q, et al. A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Res Ther 2009, 11:R180.
65. Westerberg G, Bergstrom M, Gustafson S, Lindqvist U, Sundin A, Langstrom B. Labelling of polysaccharides using [11C]cyanogen bromide. In vivo and in vitro evaluation of 11C-hyaluronan uptake kinetics. Nucl Med Biol 1995; 22(2):251-256.
66. Wu JJ, D.R. Eyre DR. Structural analysis of cross-linking domains in cartilage type XI collagen. J Biol Chem 1995; 270:18865-18870.
67. Yada T, Suzuki S, Kobayashi K, M. Kobayashi M, Hoshino T, Horie K, Kimata K, Occurrence in chick embryo vitreous humor of a type IX collagen proteoglycan with an extraordinarily large chondroitin sulfate chain and short alpha 1 polypeptide. J Biol Chem 1990; 265:6992-6999.
68. Yalovac A, Ulusu NN. Collagen and collagen disorders. FABAD J Pharm Sci 2007; 32:139-144.
69. Yamaguchi Y, Mann DM, Ruoslathi E. Negative regulation of transforming growth factor-h by the proteoglycan decorin. Nature 1990; 346:281-284.
70. Zhang LL, Wei W, Xiao F, Xu JH, Bao CD, Ni LQ, Li XF. A randomized, double-blind, multicenter, controlled clinical trial of chicken type II collagen in patients with rheumatoid arthritis. Arthritis Rheum 2008; 9(7):905-910.
71. Zhang ZJ, Lee CSY, Lider O, Weiner HL. Suppression of adjuvant arthritis in Lewis rats by oral administration of type II collagen. J Immunol 1990; 145(8):2489-2493.
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