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Joint Fluid - Description and Roles

Joint Fluid is high-molecular weight (>700 kilodaltons or kDa), purified sodium hyaluronate (hyaluronan or HA) derived by microbial fermentation.
Joint Fluid (HA) rejuvenates, rehydrates and lubricates joints.
  • HA sends signals to joint cells to maintain healthy production of synovial fluid.1
  • HA sends signals to joint cells to maintain normal structure.1
  • HA sends signals to cells in joints that support healthy maintenance of joint tissues.1
  • HA signaling effects are dependent on its size (molecular weight).1
  • HA provides lubrication for smooth movement of joints.2
  • HA reduces friction of surface cartilage and synovial fluid to aid movement of joints.2
  • HA helps distribute weight load across the joint.2
  • HA enhances shock absorption capabilities in joints.2
  • HA forms a gel in solution, holding large amounts of water (hydration).2
  • HA is essential for formation, structure and maintenance of cartilage, synovial lining and synovial fluid.3
  • HA is the “backbone” of aggrecan, the major proteoglycan in cartilage.3
  • Exogenous HA has long-lasting effects on repairing structural integrity of human joint tissues.4
  • Orally administered HA has evidence for uptake into joints and connective tissues.5
  • Orally administered HA shows preliminary evidence for joint health benefits in animals and humans.6
Joint Fluid is a mega-dalton form of Hyaluronan, the molecule that exists naturally in synovial fluid and cartilage. HA is primarily responsible for joint lubrication and ease of joint movement, as well as providing the molecular backbone of proteoglycans in cartilage that provide cushioning and resiliency properties to cartilage. Glycosaminoglycans (GAGs), especially Chondroitin, attach to the HA proteoglycan backbone to form proteoglycans (Aggrecan) in cartilage. The high charge density of Chondroitin in proteoglycans holds water and is directly responsible for the resistance to compression of cartilage tissue, critical for joint health, joint function, and mobility.

HA is a very long, linear GAG made from hundreds of repeating N-acetylglucosamine/glucuronate subunits. In solution, HA forms a large, space-filling globe that can change shapes depending on mechanical and shear forces, accounting for its rheological properties. HA has been intensively studied for its molecular signaling properties, and it turns out that these properties are highly dependent on molecular weight of HA. When HA molecular weight is high (>500 kDa), anticatabolic, anabolic and maintenance of normal physiology signals are transmitted to cells. HA with molecular weights less than 500 kDa does not possess lubricating properties, and is not long enough to form stable proteoglycans in cartilage. Moreover, small pieces of HA (termed HA oligosaccharides, under 100 kDa molecular weight) have been implicated in signaling and promoting cartilage and synovial fluid deterioration. Furthermore, HA levels decrease in size and levels with age in both synovial fluid and cartilage, resulting in less joint lubrication and resiliency.

HA is especially prone to attack by oxidative damage (free radicals), producing HA oligosaccharides. Thus, antioxidants become important for protecting HA. Since HA deterioration potentially signifies a practical and serious loss of joint lubrication and structure, it is logical that joint tissues would use HA as an important signaling molecule for homeostasis and health status. For instance, HA with molecular weights less than 500 kDa do not possess lubricating properties, and are not long enough to form stable proteoglycans in cartilage.

HA has been injected into joint synovial cavities as a medical device, and many studies and reviews have found that joint discomfort, function and structure are improved over time periods lasting a year or more, long after exogenous HA has left joints. Typically, HA injected into joints clears out of synovial fluid in less than a week. Biopsies of human joint cartilage and synovium 6-12 months after intra-articular HA administration showed partial restoration of synovial and cartilage structures. This extensive line of evidence suggests that high molecular weight HA initiated signaling cascades conducive to maintaining joint health and structure.

References

1: Akatsuka 1993a; Akatsuka 1993b; Almond 2007; Anastassiades 1984; Anonymous 2003; Asari 2000; Aviad 1994; Baker 1994; Balazs 1974; Balazs 1993; Balazs 1998; Balazs 2003; Band 2002; Belmonte 1998; Betts 1982; Betts 1984; Blundell 2002; Breborowicz 2001; Brun 2003; Bucci 2004; Camenisch 2000; Campo 2003a; Campo 2003b; Campoccia 1993; Chevrier 1982; Chichibu 1988; Chow 1995; Cleland 1969; Coleman 1999; Coleman 2000; Cortivo 1990; Cortivo 1996; Culty 1990; Culty 1992; Dahl 1985; Darzynkiewicz 1971; Day 2002; Deb 2002; Deeble 1990; Delehedde 2002; Dowthwaite 2002; Engstrom-Laurent 1985; Engstrom-Laurent 1989; Entwhistle 1996; Fieber 2004; Flannery 2002; Forrester 1977; Forrester 1980; Forrester 1981; Fox 1983; Fraser 1997; Frati 1997; Frean 2002a; Frean 2002b; Fujii 1999a; Fujii 1999b; Fujii 2001; Fukuda 1996; Fukuda 1997; Gerdin 1997; Ghosh 1992; Goldberg 1987; Goldberg 1991; Gomis 2004; Gotoh 1988; Greco 1998; Green 1990; Greenberg 2006; Greenwald 1980; Greenwald 1986; Greenwald 1991; Grootveld 1991; Hakansson 1980; Hakansson 1987; Halliwell 1985; Halliwell 1988; Harrison 2002; Hawkins 1996; Hawkins 1998; Healy 2005; Hegewald 2004; Henderson 1991; Hiro 1986; Homandberg 1997; Homandberg 2003; Homandberg 2004; Hutadilok 1988; Ialenti 1994; Ishida 1997; Julovi 2004; Kang 1999; Kato 1995; Kawasaki 1999; Kelly 2004; Kikuchi 2001; Knudson 2000; Knudson 2002a; Knudson 2002b; Knudson 2004a; Knudson 2004b; Kobayashi 1997; Kobayashi 2004; Konttinen 1991; Konttinen 2000; Lacy 1987; Larsen 1992; Laurent 1986; Laurent 1987; Laurent 1992; Laurent 1995; Laurent 1996; Laurent 2002; Lee 2000; Lesley 2002; Li 1997; Maneiro 2004; Maniwa 2001; McCord 1974; McCourt 1994; McNeil 1985; McNeil 1986; McNeil 1989; Merry 1989; Miyake 1990; Moseley 2002a; Moseley 2002b; Moseley 2003; Motohashi 1985; Murakame 1981; Myint 1987; Nakamura 2004; Neumann 1999; Nitzan 2001a; Noble 1998; Noble 2002; Nonaka 2000; Ohno-Nakahara 2004; Parkar 1998; Parkes 1991; Parsons 1994; Parsons 2002; Pawlak 2002; Phillips 1998; Pisko 1983; Polubinska 2000; Poole 1990; Presti 1994; Punzi 1989; Rees 2002; Rehakova 1994; Roberts 1987; Roberts 1989; Saari 1990; Saari 1991; Saari 1993; Sato 1988; Scott 2002; Sheehan 2003; Shen 2004; Slevin 2000; Smith 1987; Stove 2002; Strachan 1990; Suzuki 1993; Takahashi 2004; Tammi 2002; Tanaka 2004; Taylor 2006; Termeer 2002; Tibesku 2006; Tobetto 1992; Tobetto 1993; Toole 2000; Toole 2004; Turley 2002; Uchiyama 1990; Ueno 1995; Underhill 1989; Underhill 1992; van der Gaag 1987; Venge 1982; Weigel 1986; Weitz 1988; Wiebkin 1975; Williams 1997; Williams 2003; Xu 2002a; Xu 2002b; Yamazaki 2003; Yasui 1992; Zhang 2005

2: Al-Assaf 2000; Aviad 1994; Backus 2002; Baker 1989; Balazs 1968; Balazs 1974; Balazs 1993; Bell 2006; Cascone 2002; Coleman 2002; Davies 1969; Dintenfass 1966; Dowson 1969; Fraser 1997; Ghosh 1994; Gibbs 1968; Goa 1994; Hardingham 2002; Hatakeyama 2002; Haxaire 2002; Hills 1998; Hills 2000; Hlavacek 1993a; Hlavacek 1993b; Hlavacek 1995; Jay 1998; Jensen 1954; Kawai 2004; Kawano 2003; Kobayashi 2001; Kumar 2001; Laurent 1992; Laurent 1996; Levick 2002; Linn 1968a; Linn 1968b; Mabuchi 1994; Mabuchi 1999; Marshall 2000; Matsuoka 2002; Mazzucco 2004; Milas 2002; Mori 2002; Mow 1997; Nitzan 2001a; Nitzan 2001b; Ogston 1953; Pelletier 1993; Pena 2002; Preston 1965; Radin 1970a; Radin1970b; Radin 1971; Radin 1972; Roberts 1982; Scott 1991; Scott 1992; Seller 1969; Swann 1974; Swann 1984; Swanson 1969; Tadmor 2002; Vogel 2005; Vos 1969; Walker 1969; Walker 1970; Wik 1998; Wik 2002; Yokobori 1995

3: Bates 1985; Bayliss 2002; Coleman 2002; Day 1998; DeAngelis 2002; Hardingham 1972; Hardingham 1998; Hardingham 2002; Heinegard 1998; Knudson 1993; Knudson 2002; Knudson 2003; Laurent 1992; Lee 2000; Levick 2002; Nishida 1999; Rooney 2002; Scott 1992

4: Bach 2003; Dougados 1994; Dougados 2000a; Frizziero 1998; Goldberg 2005; Gossec 2004; Guidolin 2001; Guidolin 2002; Jubb 2003; Kolarz 2003; Listrat 1997; Pasquali 2001; Weiss 2002

5: Balogh 2008; Schauss 2004; Schauss 2008;

6: Bergin 2006; Bucci 2005d; Handl 2003; Kalman 2008; Martinez-Puig 2007; Pierce 2004; Stancikova 2004.
THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION.
THIS PRODUCT IS NOT INTENDED TO DIAGNOSE, TREAT, CURE OR PREVENT ANY DISEASE.