Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weightbearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability. Ann Intern Med. 2000;133:635-646. www.annals.org For author affiliations and current addresses, see end of text.

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Osteoarthritis: New Insights Part 1: The Disease and Its Risk Factors

Articular cartilage is the highly specialized connective tissue of diarthrodial joints. Its principal function is to provide a smooth, lubricated surface for articulation and to facilitate the transmission of loads with a low frictional coefficient (Figure 1). Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment. Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health.



Figure 1.

Gross photograph of healthy articular cartilage in an adult human knee.



Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist. The preservation of articular cartilage is highly dependent on maintaining its organized architecture.

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The basic science of articular cartilage: structure, composition, and function

Analysis of cellular mechanotransduction, the mechanism by which cells convert mechanical signals into biochemical responses, has focused on identification of critical mechanosensitive molecules and cellular components. Stretch-activated ion channels, caveolae, integrins, cadherins, growth factor receptors, myosin motors, cytoskeletal filaments, nuclei, extracellular matrix, and numerous other structures and signaling molecules have all been shown to contribute to the mechanotransduction response. However, little is known about how these different molecules function within the structural context of living cells, tissues, and organs to produce the orchestrated cellular behaviors required for mechanosensation, embryogenesis, and physiological control. Recent work from a wide range of fields reveals that organ, tissue, and cell anatomy are as important for mechanotransduction as individual mechanosensitive proteins and that our bodies use structural hierarchies (systems within systems) composed of interconnected networks that span from the macroscale to the nanoscale in order to focus stresses on specific mechanotransducer molecules. The presence of isometric tension (prestress) at all levels of these multiscale networks ensures that various molecular scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response. Future research in this area will therefore require analysis, understanding, and modeling of tensionally integrated (tensegrity) systems of mechanochemical control.

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Cellular mechanotransduction: putting all the pieces together again.

Forces in Joints, Skeletal Biology, Analysis of Bone Remodeling, Mechanical Properties of Bone, Fatigue and Fracture Resistance of Bone, Mechanical Adaptation of the Skeleton, Synovial Joint Mechanics, Mechanical Properties of Ligament and Tendon

Skeletal Tissue Mechanics

Over the past decade, since it was first observed in vivo, there has been an explosion in interest in the thin (∼500 nm), gel-like endothelial glycocalyx layer (EGL) that coats the luminal surface of blood vessels. In this review, we examine the mechanical and biochemical properties of the EGL and the latest studies on the interactions of this layer with red and white blood cells. This includes its deformation owing to fluid shear stress, its penetration by leukocyte microvilli, and its restorative response after the passage of a white cell in a tightly fitting capillary. We also examine recently discovered functions of the EGL in modulating the oncotic forces that regulate the exchange of water in microvessels and the role of the EGL in transducing fluid shear stress into the intracellular cytoskeleton of endothelial cells, in the initiation of intracellular signaling, and in the inflammatory response.

https://www.annualreviews.org/doi/pdf/10.1146/annurev.bioeng.9.060906.151959

The Structure and Function of the Endothelial Glycocalyx Layer

Swelling of articular cartilage depends on its fixed charge density and distribution, the stiffness of its collagen-proteoglycan matrix, and the ion concentrations in the interstitium. A theory for a tertiary mixture has been developed, including the two fluid-solid phases (biphasic), and an ion phase, representing cation and anion of a single salt, to describe the deformation and stress fields for cartilage under chemical and/or mechanical loads. This triphasic theory combines the physico-chemical theory for ionic and polyionic (proteoglycan) solutions with the biphasic theory for cartilage. The present model assumes the fixed charge groups to remain unchanged, and that the counter-ions are the cations of a single-salt of the bathing solution. The momentum equation for the neutral salt and for the intersitial water are expressed in terms of their chemical potentials whose gradients are the driving forces for their movements. These chemical potentials depend on fluid pressure p, salt concentration c, solid matrix dilatation e and fixed charge density cF. For a uni-uni valent salt such as NaCl, they are given by mu i = mu io + (RT/Mi)ln[gamma 2 +/- c(c + cF)] and mu w = mu wo + [p-RT phi (2c + cF) + Bwe]/pwT, where R, T, Mi, gamma +/-, phi, pwT and Bw are universal gas constant, absolute temperature, molecular weight, mean activity coefficient of salt, osmotic coefficient, true density of water, and a coupling material coefficient, respectively. For infinitesimal strains and material isotropy, the stress-strain relationship for the total mixture stress is sigma = - pI-TcI + lambda s(trE)I + 2 musE, where E is the strain tensor and (lambda s, mu s) are the Lame constants of the elastic solid matrix. The chemical-expansion stress (-Tc) derives from the charge-to-charge repulsive forces within the solid matrix. This theory can be applied to both equilibrium and non-equilibrium problems. For equilibrium free swelling problems, the theory yields the well known Donnan equilibrium ion distribution and osmotic pressure equations, along with an analytical expression for the "pre-stress" in the solid matrix. For the confined-compression swelling problem, it predicts that the applied compressive stress is shared by three load support mechanisms: 1) the Donnan osmotic pressure; 2) the chemical-expansion stress; and 3) the solid matrix elastic stress. Numerical calculations have been made, based on a set of equilibrium free-swelling and confined-compression data, to assess the relative contribution of each mechanism to load support. Our results show that all three mechanisms are important in determining the overall compressive stiffness of cartilage.

A triphasic theory for the swelling and deformation behaviors of articular cartilage.

The objective of this study is to establish and verify the set of boundary conditions at the interface between a biphasic mixture (articular cartilage) and a Newtonian or non-Newtonian fluid (synovial fluid) such that a set of well-posed mathematical problems may be formulated to investigate joint lubrication problems. A "pseudo-no-slip" kinematic boundary condition is proposed based upon the principle that the conditions at the interface between mixtures or mixtures and fluids must reduce to those boundary conditions in single phase continuum mechanics. From this proposed kinematic boundary condition, and balances of mass, momentum and energy, the boundary conditions at the interface between a biphasic mixture and a Newtonian or non-Newtonian fluid are mathematically derived. Based upon these general results, the appropriate boundary conditions needed in modeling the cartilage-synovial fluid-cartilage lubrication problem are deduced. For two simple cases where a Newtonian viscous fluid is forced to flow (with imposed Couette or Poiseuille flow conditions) over a porous-permeable biphasic material of relatively low permeability, the well known empirical Taylor slip condition may be derived using matched asymptotic analysis of the boundary layer at the interface.

Boundary Conditions at the Cartilage-Synovial Fluid Interface for Joint Lubrication and Theoretical Verifications

Many hydrated soft tissues, such as articular cartilage, meniscus and intervertebral disc, change their dimensions, volume and weight when the ion concentration in the external bathing solution is changed (Parsons and Black 1979; Maroudas 1975, 1979; Maroudas and Bannon 1981; Myers et al 1984; Mow and Schoonbeck 1984; Eisenberg and Grodzinsky 1985, 1987) For example, for an unloaded specimen of cartilage soaked in NaCl solutions at constant temperature, the tissue dimensions decrease nonlinearly in an exponential manner with increasing NaCl concentration; this decrease approaches an asymptote at a high concentration, eg, 25M NaCl (Mow and Schoonbeck 1984) Therefore, at the physiological state of 015M NaCl, cartilage is in a swollen state, with a swelling pressure resisted by the elastic stress developed in the collagen-proteoglycan solid matrix This is often referred to as the collagen pre-stress or elastic stress in the solid matrix (Maroudas 1975, 1976, 1979; Maroudas and Bannon 1981; Grodzinsky et al 1981) For a normal cartilage bathed in 015M NaCl solution, the swelling pressure has been measured to be around 017 MPa (Maroudas 1975,1979; Maroudas and Bannon 1981)

J. S. Hou

Papers

A triphasic theory for the swelling and deformation behaviors of articular cartilage.

Boundary Conditions at the Cartilage-Synovial Fluid Interface for Joint Lubrication and Theoretical Verifications

Triphasic Theory for Swelling Properties of Hydrated Charged Soft Biological Tissues