Hyaluronic Acid’s Biomechanical

Stabilization Function in the

Hyaluronic acid is one of the components of syno- of the temporomandibular joint are the disk joint, the
vial fluid. According to what is already well known retro-disk tissue, the temporomandibular ligament,
in national and international biomedical literature, the disk lateral ligament, the synovial membrane,
hyaluronic acid in the context of the TMJ serves and synovial fluid. Our proposal for this work was to
two important biomechanical tasks. The first is focus the proper role played by synovial fluid and in
feeding the articular cartilage; the second is lubri- particular by hyaluronic acid as a biomechanical re-
cating the components of the joint. These two func- straint. Also studied was the role played by synovial
tions served by the same element change each other fluid in feeding joint cartilage and lubricating articu-
according to the continuous alternation of values of lar components in the articular cavity. These two
pressure in the articular cavity. functions are well-studied in the literature, which
considers hyaluronic acid the main component that
The authors propose to overcome this state-
serves those functions. The primary purpose of our
ment by demonstrating that hyaluronic acid plays a
work was to understand how two such disparate
third function in the TMJ, which is the biomechan-
functions, such as feeding joint fibrocartilage and the
ical function of stabilizing the articular compo- mechanical function of lubrication are guaranteed by
nents. hyaluronic acid. This study led us to understand the
basic double biomechanical role played by this pro-
Key Words: Hyaluronic acid, synovial fluid tein molecule in the temporomandibular joint, which
is lubrication and stabilization.
We believe that this may become a very inter-

T
he proper functional and postural connec- esting field on which to indagate about the patho-
tion among the temporomandibular joint genic mechanisms of temporomandibular joint dis-
components is controlled by some anatomic order.
structures that play the role of biomechan-
ical restraints that drive and at the same time condi- DISCUSSION
tion the complex joint movements. To simplify the mong the components of synovial fluid, hyal-
conception of biomechanical restraint, Osborn, with
an enlightened example, says that a body on which
A uronic acid is the one that serves many impor-
tant functions and is also the one that determines the
some biomechanical restraints work does not neces- physical and functional features of synovial fluid.
sarily move according to the direction chosen by the The concentration of hyaluronic acid in the synovial
forces applied to it; in fact, he also says that no matter fluid determines its viscosity, which is considered a
which direction forces operate on a door, it can only sign of articular health.
open or close in the direction dictated by the hinges In 1939 Mayer was the first to identify it in sy-
(Osborn, 1989). The known biomechanical restraints novial fluid. Hyaluronic acid is a glycosaminoglycan
made of the periodic repeat of d-glucuronic acid and
n-acetylglucosamine disaccharides units. Its molecu-
Universita Degli Studi di Roma, “La Sapienza,” Cattedra di
Chirurgia Maxillo-Facciale, Director Prog. Giorgio Ianetti; and
lar weight changes from side to side; in fact, hyal-
Universita di Siena, Dipartmento di Scienze Biologiche, Italy. uronic acid is omnipresent and plays different roles
Address correspondence to Aboh Ikenna Valentine, Via Alto such as support, cicatrization, and regulation of the
31/E 00050, Roma; E-mail: aboh [email protected] fluid’s flux. The fibroblastic cells of synovial mem-

751
THE JOURNAL OF CRANIOFACIAL SURGERY / VOLUME 13, NUMBER 6 November 2002

brane, called B synoviocytes, synthesize the hyal- among the various components of synovial fluid
uronic acid as well as other components of the syno- whose physical and chemical features allow it to ab-
vial fluid: fibronectin, laminin, collagenous fibers solve both mechanical and trophic tasks.
type I and III, proteases and their inhibitors, inter- To understand how lubrication occurs we must
leukin 1, proteoglycans, and lubricating glycopro- remember that the polysaccharide chains are kept
tein-1 (LPG1). Hyaluronic acid is bound with other folded on each other by hydrogen bridges existing
proteins of synovial fluid and forms a layer (1–2 ␮m) among the hexoses as bowstrings. When an articula-
between the joint cartilage and the joint cavity. This tion is moved, that is to say when energy is applied
film is not only distributed on the surface of the car- to the polysaccharide chain of hyaluronic acid, the
tilage but also goes deep inside. One of the most hydrogen bridges break and the energy produced by
important functional features of hyaluronic acid is its this is used to create new hydrogen bridges between
capacity to effect different and particular space con- other hexose pairs in another point of the chain. This
formations. The length of the mucopolysaccharide allows the spheroidal molecules to penetrate inside
chain allows this capacity. Once the long chains enter each other and to reduce their measures to allow not
the synovial fluid they tend to wrap themselves up, only sliding but amortization also. The other impor-
penetrating each other and folding reciprocally. tant role hyaluronic acid plays is to feed the articular
In theory 0.33 mg of hyaluronic acid is enough cartilage.
to saturate 1 mL solution, but the true concentration Synovial fluid with its component, hyaluronic
of hyaluronic acid is 3 mg/mL. This depends on the acid in primis, is a good vehicle for carryign oxygen,
fact that, once in the liquid, the molecules wrap glucose, and other nutrients from the vascular sys-
themselves up interpenetrating each other and fold- tem of the synovial membrane to the articular carti-
ing reciprocally. lagem, which is not vascularized. Synovial fluid is
In the context of the synovial fluid hyaluronic also able to protect the joint cartilage. Therefore the
acid performs two basic tasks: it feeds the joint fibro- mechanism of feeding the articulation’s fibrocarti-
cartilage and performs the mechanical work of lubri- lage is deeply connected with the increase in pres-
cating the articular surfaces. Hyaluronic acid is able sure inside the articulation, which allows the spread
to serve both of these functions because of its intrin- of synovial fluid and in particular of hyaluronic acid
sic ability to effect alternately a linear and spheroidal inside the extracellular matrix of articular cartilage,
conformation depending on the pressures in the ar- ensuring the exchange of nutrients with the cells.
ticular cavity. Once again we feel it necessary to focus on the inti-
Intra-articular pressures greater than atmo- mate relation between the physical and chemical fea-
spheric pressure make the molecules of hyaluronic tures of hyaluronic acid, its functional role in the
acid lose their spheroidal form and deeply penetrate context of the temporomandibular joint on one hand
inside the joint’s fibrocartilage; in this way trophic and on the other the changing pressures that exist in
function is encouraged. When pressure is less than the articular cavity, depending on how the articula-
atmospheric pressure, the proteins lose their deep tion is flexed.
contact with the surface of the joint cartilage, so they An important contribution about the pressure in
assume the spheroidal conformation to better allow the joint cavity comes from Nitzan’s study in 1992.
the sliding of articular surfaces against each other. She recorded the intra-articular pressure changes
These changes happen during the different during mandibular movements. According to our
phases of the mastication. During the compression of studies we believe that lubrication and feeding are
chewed food, under the pressure of the elevator hyaluronic acid’s biomechanical role, which changes
muscle of the mandible, the pressure in the articular with the cycle of mastication and the consequent
cavity increases and makes the protein macromol- change of intra-articular pressure. But we also be-
ecules penetrate into the cellular matrix of the hya- lieve that the biomechanical role of hyaluronic acid is
line cartilage to allow feeding of the cartilage itself. not only to lubricate the joint surfaces but also to
During rapid mandibular movement when no stabilize the structural components of the temporo-
force is used and when the mandible is at rest, the mandibular joint. In fact what we know is that when
pressure in the articular cavity is negative. This en- the pressure inside the cavity is high (for example,
courages lubrication, allowing the articular surfaces during the mastication of chewed food) the macro-
to slide against each other, so as to let the mandible molecule chains penetrate into the intercellular ma-
move in any direction. trix of cartilaginoid structures. We think this mecha-
It is now easy to understand the functional du- nism has a biomechanical role, in fact: creating
alism of the hyaluronic acid, which is the only one structural bridges among the different articular com-

752
 HYALURONIC ACID’S BIOMECHANICAL STABILIZATION FUNCTION / Cascone et al

ponents, hyaluronic acid promotes anatomical inte- alteration of the physiological pressure will determi-
gration of those structures that otherwise with nega- nate an incoordination of the biomechanical function
tive pressure will be distinct and fluent. Obviously of hyaluronic acid, thus provoking functional deficit
any increase of intra-articular pressure or any alter- of the whole TMJ.
ation of the physiological movement can produce (or
be the “primum movens”) a deterioration of this im- SUGGESTED READING
portant function and generate a pathology that can Banes AJ, Link GW, Bevin AG, et al. Tendon synovial cells secrete
prevent the feeding of articular cartilage or even the fibronectin in vivo and in vitro. J Orthop Res 1988;6:73
physiological sliding of the various intra-articular Cascone P, Vetrano S, Nicolai G. Le restrizioni biomeccaniche dell’
anatomic components. A.T.M. II legamento tempo-mandibolare. Dental Cadmos,
1998
Dijkgraaf LC, De Bont LGM, Geert B, et al. Function, biochemistry
CONCLUSIONS and metabolism of the normal inovila membrane of the tem-
poro-mandibular joint. J Oral Maxillofac Surg 1996;54:95–100
he present state of studies concerning the tempo- Dorrit W. Nitzan, DMD, Yona Mahler, PhD, +
T romandibular joint states that hyaluronic acid is
an important component of synovial fluid and also,
Fox RI, Kang H. Structure and function of synoviocytes. In: Mc-
Carty DJ, Koopman WJ, eds. Arthritis and allied conditions.
Textbook of Rheumatology. 12th ed. Philadelphia: Lea & Fe-
in the context of the TMJ, it plays two main functions biger; 1993: 263–278
Gadially FN. Fine structure of synovial joint. London, England:
that depend on pressure inside the articular cavity. Butterworths; 1983: 1–41
One of these is the biomechanical function of lubri- Gatter RA. A practical handbook of joint fluid analysis. Philadel-
cating articular surfaces; the other is feeding the ar- phia: Lea & Febiger; 1984: 3
ticular cartilage. When intra-articular pressure Gotoh S, Onaya JI, Mayummi A, et al. Effects of the molecular
weight of hyaluronic acid and its action mechanism on experi-
achieves subatmospheric values, the proteins lose mental joint pain in rats. Ann Rheum Dis 1993;52:187
their deep contact with the cartilaginoid articular Hatton MN, Swann DA. Studies on bovine temporomandibular
surface and with the extracellular matrix and they joint synovial fluid. J Prosthet Dent 1986;56:635–638
assume a spherical form to allow movement of the Henderson B, Edwards JCW. The synovial lining: In Health and
Disease. London, England: Chapman and Hall; 1987: 41–71
articulation. Hills BA, Butler BD. Surfactants identified in synovial fluid and
Vice versa, when intra-articular pressure their ability to act as boundary lubricants. Ann Rheum Dis
achieves greater than atmospheric values we can ob- 1984;43:641–648
serve the penetration of hyaluronic acid inside the Hou JS, Mow VC, Lai WM, et al. An analysis of the squeeze-film
lubrication mechanism for articular cartilage. J Biomech 1992;
extracellular matrix of fibrocartilage. At first this be- 25:247–259
havior was connected only to the trophic function. In Kobayashi Y, Okamoto A, Nishinari K. Viscoelasticity of hyal-
fact at that pressure, because of their physical and uronic acid with different molecular weights. Biorheology
31:235, 1994
chemical features, hyaluronic acid’s proteins pen-
Laurent UBG, Reed RK. Turnover of hyaluronan in the tissues.
etrate the articular cartilage, allowing the entrance of Advanced Drug Delivery Rev 1991;7:237
nutrients, thus serving the function of feeding al- Leardini G, Ramonda R. Le caratteristiche fisico-chimiche e le fun-
ready known by medical literature. Yet our studies zioni del liquido sinoviale. Reumatismo 1996; 48, I (Suppl. N.
2):
allow us to state that hyaluronic acid plays a third Levik JR, MacDonald JN. fluid movement across synovium in
function in the TMJ context, which is mechanical sta- healthy joints: role of synovial fluid macromolecules. Ann
bilization of articular components, and all this hap- Rheum Dis 52:187, 1995
pens at those pressures that promote hyaluronic ac- Linn FC. Lubrication of animal joints. I. The anthrotripsometer. J
Bone Joint Surg 49-A, 1079 1098, 1967
id’s trophic function. Linn FC, Radin EL. Lubrication of animal joints. III. The effects of
In fact when the intra-articular pressure is posi- certain Chemical alterations of the cartilage and lubricant Ar-
tive, the proteins penetrate the cellular matrix with thrit Rheum 11:674–682, 1968
their molecular structures, making a strong biome- Maroudas A. Studies on the formation of hyaluronic acid films.
Lubrication and wear in joints (Ed. Wright V), pp. 124–133.
chanical bond among the various components that Sector, London, 1969
otherwise at negative pressure will be separated. Maroudas A. Fluid transpoert in cartilage. Ann Rheum Dis 34
This process promotes mechanical stabilization of ar- (suppl. 2), 77–81, 1975.
ticular components during the compression of McCutchen CW. Mechanism of animal joints. Sponge-hydrostatic
and weeping bwerings. Nature, London 184:1284–1285, 1959
chewed food. During the physiological variation of McCutchen CW. The frictional properties of animal joint. Wear
the temporomandibular dynamic function, the con- 5:1–17, 1962
tinuous change of pressure inside the articular cavity McCutchen CW. Boundary lubrication by synovial fluid: demon-
stration and possible osmotic explanation. Fed Proc Fed Am
permits alternation of the three functions. The fine Soc Exp Biol 25:1061–1068, 1966
equilibrium of pressure in the articular cavity of the Mejer K, Palmer JW. The polysaccharide of the vitreous humor. J
temporomandibular joint allows us to state that any Biol Chem 1934;107:629

753
THE JOURNAL OF CRANIOFACIAL SURGERY / VOLUME 13, NUMBER 6 November 2002

Mejer K, Smyth EM, Dawson MH. The isolation of a mucopolysac- surface of normal porcine type B synoviocytes in vitro. Arthri-
charide from synovial fluid. J Biol Chem 128:319, 1939 tis Rheum 1985:28;1105
Mohl ND. Functional anatomy of the temporomandibular joint. Swann DA, Radin EL, Nazimiec M, et al: Role of normal hyal-
The president’s conference on the examination, Diagnosis and uronic acid in joint lubrication. Ann Rheum Dis 1974;33:318
Management of Temporomandibular Disorders, (eds Laskin D Swann DA, Hendren RB, Radin EL, et al. The lubricating activity
et al.), 3–12. American Dental Association, Chocago, IL of synovial fluid glycoproteins. Arthritis Rheum 24:22–30,
Nickel JC, McLachlan KR. In vitro measurement of the frictional 1981
properties of the temporomandibular joint disc. Archs Oral Swann DA. Structure and function of lubricin, the glycoprotein
Biol Vol 39, N°4, pp. 323–331, 1994 responsible for the boundary lubrication articular cartilage.
Nitzan DW, Maheler Y, Simkin A. Intra-articular pressure mea- Articular Synovicum Internationale Symposium. Basel:
surements in patients with suddenly developing, severely lim- Bruges P Fraachimont & S Kerger Ed; 1981
ited mouth opening. J Oral Maxillofac Surg 50:1038–1042, 1992 Swann DA, Blochh KJ, Swindell D, et al. The lubricating activity of
Radin EL, Swann DA, Weisser PA. Separation of hyaluronate free
human synovial fluid. Arthritis Rheum 1984; 27: 552–556
lubricating fraction from synovial fluid. Nature 228:377, 1970
Roth TE, Goldberg JS, Behrents RG. Synovial fluid pressure de- Swanson SAV. Friction, wear and lubrication. In: Forrmann MAR,
termination in the temporo-mandibular joint. Oral Surg Oral ed. Adult Auricular cartilage 2nd ed. London: Pitman Medi-
Med Oral Path 1984;57:583 cal; 1979: 415–460
Scapino RP. The posterior attachment: Its structure, function and Todesco S, Gambari PF. Malattie Reumatiche. New York: McGraw
appearance in TMJ imaging studies. Part 2.J. Craniomandib Hill; 1993: 8–9,
Disord Facial Oral Pain, 5:155, 1991 Tulamo RM, Heiskanen T, Salonen M. Concentration and molecu-
Simkin PA. Synovial Physiology. In: McCarty DJ, Koopman WJ, lar weight distribution of hyaluronate in synovial fluid from
eds. Arthritis and Allied Conditions. A Textbook of Rheuma- clinically normal horses and horses with diseased joint. An J
tology. 12th ed. Philadelphia, PA: Lea & Febiger; 1993:1993 Vet Res: 55:710, 1994
Singer II, Kazakis DM, Kawka DH, et al: Extracellular matrix- Westesson PL. Double contrast arthrography and internal de-
cytoskeletal interactions in rheumatoid arthritis. I. Immuno- rangement of the temporomandibular joint. Swedish Dental
electron microscopic analysis of the fibronexus at the adhesive Journal Suppl. 13, 1982

754