Lubrication Of Synovial Joints Research Articles

Brushing Up on Cartilage Lubrication: Polyelectrolyte-Enhanced Tribological Rehydration.

This study presents new insights into the potential role of polyelectrolyte interfaces in regulating low friction and interstitial fluid pressurization of cartilage. Polymer brushes composed of hydrophilic 3-sulfopropyl methacrylate potassium salt (SPMK) tethered to a PEEK substrate (SPMK-g-PEEK) are a compelling biomimetic solution for interfacing with cartilage, inspired by the natural lubricating biopolyelectrolyte constituents of synovial fluid. These SPMK-g-PEEK surfaces exhibit a hydrated compliant layer approximately 5 μm thick, demonstrating the ability to maintain low friction coefficients (μ ∼ 0.01) across a wide speed range (0.1-200 mm/s) under physiological loads (0.75-1.2 MPa). A novel polyelectrolyte-enhanced tribological rehydration mechanism is elucidated, capable of recovering up to ∼12% cartilage strain and subsequently facilitating cartilage interstitial fluid recovery, under loads ranging from 0.25 to 2.21 MPa. This is attributed to the combined effects of fluid confinement within the contact gap and the enhanced elastohydrodynamic behavior of polymer brushes. Contrary to conventional theories that emphasize interstitial fluid pressurization in regulating cartilage lubrication, this work demonstrates that SPMK-g-PEEK's frictional behavior with cartilage is independent of these factors and provides unabating aqueous lubrication. Polyelectrolyte-enhanced tribological rehydration can occur within a static contact area and operates independently of known mechanisms of cartilage interstitial fluid recovery established for converging or migrating cartilage contacts. These findings challenge existing paradigms, proposing a novel polyelectrolyte-cartilage tribological mechanism not exclusively reliant on interstitial fluid pressurization or cartilage contact geometry. The implications of this research extend to a broader understanding of synovial joint lubrication, offering insights into the development of joint replacement materials that more accurately replicate the natural functionality of cartilage.

Mathematical Model to Study the Squeeze Film Characteristics of Diseased Human Synovial Knee Joint

Synovial fluid functions as a biological lubricant and lubricates articular cartilage to reduce friction and wear. Lubricin and hyaluronic acid are the primary components of synovial fluid responsible for its lubricating properties. The loss of properties in synovial fluid and articular cartilage due to aging and activities can restrict mobility in synovial joints, resulting in the degradation of articular cartilage and ultimately leading to pathological synovial joints, which is a major cause of disability. Thus, research on synovial joints remains crucial, and despite previous investigations on synovial joint lubrication, there are several issues related to squeeze film lubrication that require further attention. The Newtonian model of squeeze film lubrication in synovial joints needs to be extensively studied. In this study, lubrication and other related properties of synovial fluid are studied theoretically. In this paper, we have studied the flow of synovial fluid in the diseased synovial joint. Further, we have studied the effect of the viscosity of the synovial fluid, the permeability of articular cartilage, thickness of articular cartilage, and fluid film thickness on the characteristic of the squeeze film formed between the articular cartilages of the diseased human knee joint. The flow of synovial fluid is modeled by considering it as a viscous, incompressible and Newtonian fluid. We have derived the modified Reynolds equation using the principle of hydrodynamic lubrication and continuum mechanics theory and solved it by applying the suitable boundary conditions according to the physical considerations. Subsequently, we obtained the expression for pressure distribution in fluid film, load-bearing capacity, and squeeze time and have done the theoretical analysis on these properties for different parameters. Pressure increases with squeeze velocity and viscosity of the synovial fluid and decreases with permeability and fluid film thickness. Human knee joint becomes diseased due to excessive pressure, and the mobility of the knee joint decreases. The load capacity increases with viscosity and squeeze velocity and decreases with permeability resulting in the reduction of the load-carrying capacity of the knee joint in diseased conditions. Moreover, the squeeze time also increased in the diseased state of the joint.

Effect of Significant Parameters on Squeeze Film Characteristics in Pathological Synovial Joints

Synovial joints are unique biological tribo-systems that allow for efficient mobility. Most of the synovial joint activities in the human body are accomplished due to the presence of synovial fluid. As a biological lubricant, synovial fluid lubricates the articular cartilage to minimize wear and friction. The key components of synovial fluid that give it its lubricating ability are lubricin, hyaluronic acid (HA), and surface-active phospholipids. Due to age and activities, synovial fluid and articular cartilages lose their properties, restricting synovial joint mobility and resulting in articular cartilage degradation, leading to the pathological synovial joint, which is a major cause of disability. In this context, synovial joint research remains significant. Even though synovial joint lubrication has been investigated, several problems linked to squeeze film lubrication need greater attention. The Newtonian model of squeeze film lubrication in synovial joints must be studied more extensively. This work aims to investigate squeeze film lubrication in diseased synovial joints. The lubrication and other properties of synovial fluid and the flow of synovial fluid in a diseased human knee joint are investigated theoretically in this work. We have investigated the effect of the synovial fluid viscosity and the effects of permeability and thickness of articular cartilage on squeeze film properties. Moreover, we have also investigated the effect of squeeze velocity and film thickness on the characteristics of the squeeze film formed between the articular cartilages of a diseased human knee joint. In this work, the articular cartilages were treated as a rough, porous material, and the geometry was approximated as parallel rectangular plates, while the synovial fluid flow is modeled as a viscous, incompressible, and Newtonian fluid. The modified Reynolds equation is obtained using the principles of hydrodynamic lubrication and continuum mechanics, and it is solved using the appropriate boundary conditions. The expressions for pressure distribution, load-bearing capacity, and squeezing time are then determined, and theoretical analysis for various parameters is conducted. Pressure is increased by squeeze velocity and viscosity, while it is decreased by permeability and film thickness, leading to an unhealthy knee joint and a reduction in knee joint mobility. The load capacity of the knee joint decreases with permeability and increases with viscosity and squeezing velocity, resulting in a reduction in the load-carrying capacity of the knee joint in diseased conditions. Synovial knee joint illness is indicated by increased pressure and squeeze time. The squeeze film properties of synovial joints are important for maintaining joint health and function. Joint diseases such as osteoarthritis, rheumatoid arthritis, and gout can affect the composition and production of synovial fluid, leading to changes in squeeze film properties and potentially causing joint damage and pain. Understanding these relationships can help in the development of effective treatments for joint diseases.

Tribo-corrosive behavior of additive manufactured parts for orthopaedic applications

BackgroundAdditive manufacturing (AM) being an integral component of the production offers a wide variety of applications in the production of different components. The medical industry after the introduction of Additive Manufacturing has resulted in several advancements. The production of intricate patient-specific implants is one of such advancements which greatly assist a surgeon during a surgery. Orthopedic implants apart from possessing good mechanical strength are also expected to exhibit good tribological and corrosion behavior. As a result, the development of various orthopaedic implants and tools has become simple with the use of additive manufacturing. Objectives and RationaleIn the current paper an effort has been made to discuss actual scientific knowledge on the tribo-corrosive behavior of additive manufactured parts for orthopedic applications. Different studies dealing with the mechanisms of lubrication and friction in synovial joints have also been considered. A special focus has also been laid down to study the corrosive effect of implants on the human body. A section dedicated to texturing of orthopedic implants has also been provided. The paper further elaborates the different research challenges and issues related to the use of additive manufacturing for the production of optimized orthopedic implants. ConclusionThe study revealed that additive manufacturing has greatly aided in the manufacture of different orthopaedic implants with enhanced properties. However, a detailed study of the effect of processes like friction, wear, lubrication and corrosion in these implants needs to be done. The performance of these implants in the presence of various synovial fluids also needs to be addressed. However, the lack of more biocompatible materials, scalability and cost issues hinder the widespread use of AM in the different orthopaedic applications.

Bioinspired Polysaccharide-Derived Zwitterionic Brush-like Copolymer as an Injectable Biolubricant for Arthritis Treatment.

Developing highly efficient and biocompatible biolubricants for arthritis treatment is extraordinarily demanded. Herein, inspired by the efficient lubrication of synovial joints, a paradigm that combines natural polysaccharide (chitosan) with zwitterionic poly[2-(methacryloyloxy) ethyl phosphorylcholine] (PMPC), to design a series of brush-like Chitosan-g-PMPC copolymers with highly efficient biological lubrication and good biocompatibility is presented. The Chitosan-g-PMPC copolymers are prepared via facile one-step graft polymerization in aqueous medium without using any toxic catalysts and organic solvents. The as-prepared Chitosan-g-PMPC copolymers exhibit very low coefficient of friction (μ < 0.01) on Ti6 Al4 V alloy substrate in both pure water and biological fluids. The superior lubrication is attributed primarily to the hydrated feature of PMPC side chains, interface adsorption of copolymer as well as to the hydrodynamic effect. In vivo experiments confirm that Chitosan-g-PMPC can alleviate the swelling symptom of arthritis and protect the bone and cartilage from destruction. Due to their facile preparation, distinctive lubrication properties, and good biocompatibility, Chitosan-g-PMPC copolymers represent a new type of biomimetic lubricants derived from natural biopolymer for promising arthritis treatment and artificial joint lubrication.

Hydration Lubrication in Biomedical Applications: From Cartilage to Hydrogels.

ConspectusIn the course of evolution, nature has achieved remarkably lubricated surfaces, with healthy articular cartilage in the major (synovial) joints being the prime example, that can last a lifetime as they slide past each other with ultralow friction (friction coefficient μ = the force to slide surfaces past each other/load compressing the surfaces < 0.01) under physiological pressures (up to 10 MPa or more)). Such properties are unmatched by any man-made materials. The precise mechanism of low friction between such sliding cartilage tissues, which is closely related to osteoarthritis (OA), the most widespread joint disease, affecting hundreds of millions worldwide, has been studied for nearly a century, but is still not fully understood. Traditionally, the roles of load bearing by interstitial fluid within the cartilage bulk and that of thin exuded fluid films at the interface between the sliding cartilage surfaces have been proposed as the main lubrication mechanism. More recent work, however, suggests that molecular boundary layers at the surfaces of articular cartilage and other tissues play a major role in their lubrication. In particular, in recent years hydration lubrication has emerged as a new paradigm for boundary lubrication in aqueous media based on subnanometer hydration shells which massively reduce frictional dissipation. The vectors of hydration lubrication include trapped hydrated ions, hydrated surfactants, biological macromolecules, biomimetic polymers, polyelectrolytes and polyzwitterionic brushes, and close-packed layers of phosphatidylcholine (PC) vesicles, all having in common the exposure of highly hydrated groups at the slip plane. Among them, vesicles (or bilayers) of PC lipids, which are the most widespread lipid class in mammals, are exceptionally efficient lubricating elements as a result of the high hydration of the phosphocholine headgroups they expose. Such lipids are ubiquitous in joints, leading to the proposal that macromolecular surface complexes exposing PC bilayers are responsible for the remarkable lubrication of cartilage. Cartilage, comprising ∼70% water, may be considered to be a complex biological hydrogel, and studying the frictional properties of hydrogels may thus provide new insights into its lubrication mechanisms, leading in turn to novel, highly lubricious hydrogels that may be used in a variety of biomedical and other applications. A better understanding of cartilage lubrication could moreover lead to better treatments for OA, for example, through intra-articular injections of appropriate lubricants or through the creation of low-friction hydrogels that may be used as tissue engineering scaffolds for diseased cartilage.In this Account, we begin by introducing the concept and origin of hydration lubrication, extending from the seminal study of lubrication by hydrated simple ions to more complex systems. We then briefly review different modes of lubrication in synovial joints, focusing primarily on boundary lubrication. We consider modes of hydrogel lubrication and different kinds of such low-friction synthetic gels and then focus on cartilage-inspired, boundary-lubricated hydrogels. We conclude by discussing challenges and opportunities.

Assessing the friction properties of synovial joint lubrication by tracking pendulum motion

Assessing the friction properties of synovial joint lubrication by tracking pendulum motion

The effect of deactivated phospholipids on joints lubrication: Osteoarthritis and lubricating properties

PLs bilayers coating the major synovial joints such as knees and hips as the lubricant are responsible for the lubrication of articular cartilage. Lamellar-repulsive effect has been considered as a lubrication mechanism but it is likely that lubricin and hyaluronan with PLs participate in the lubrication process. The molecules of lubricin and hyaluronan adsorbed by PLs have a supportive role and provide the efficient lubrication of synovial joints via the hydration mechanism (~ 80% water content). Lipid profiles of injured and healthy knees’ synovial fluids show significant differences. The phospholipid content in synovial fluid (SF) during joint inflammation, osteoarthritis is significantly higher (2 to 3 times) above the normal concentration of PL, and has a poor boundary-lubricating ability because of deactivated PL molecules. Deactivated PL molecule has no ability to form bilayers, lamellar phases, and liposomes.

Hyaluronic acid\u2013lipid binding

BackgroundPhospholipid (PL)–hyaluronic acid (HA) interactions are relevant to aging-associated vitreous humor liquefaction, therapies for dry eye disease, skin-care products and synovial joint lubrication. Phosphatidyl choline–HA interactions have been well characterized. However, other major lipids found in tears, vitreous humor and synovial joints have not. The purpose of this study was to bridge this gap of knowledge.MethodsHA (1600 kDa) at 5 mg/mL, was mixed with various lipids ranging in concentration from 0.1 to 10 mg/mL in D2O. HA–PL binding was measured from the decrease in HA proton resonance intensity with binding using a nuclear magnetic resonance spectrometer.ResultsCholesterol weakly bound to HA, followed by monoglyceride and palmitoyl palmitate < phosphatidyl choline, phosphatidic acid and sphingomyelin. The maximum amount of PL bound was 14 ± 1 µmoles inferring a 1 to 1 molar ratio of bound PL to HA dimer. Monoglyceride and palmitoyl palmitate required two to three times more lipid to achieve 100% bound HA compared to PL.ConclusionsPhysiological levels of HA, phosphatidyl choline and sphingomyelin would result in only 4% of the hydrophobic hydrogens of HA to be bound. HA–PL binding interactions could be important for therapeutic use of HA in eye drops in future studies to treat dry eye and to trap PL entering the VH to keep them from forming light scattering micelles. HA–lipid binding may also be relevant to the therapeutic effects of topical skin-care products. Both head group and hydrocarbon chain moieties influence HA–lipid interactions.

Finite Element Implementation of Biphasic-Fluid Structure Interactions in febio.

In biomechanics, solid-fluid mixtures have commonly been used to model the response of hydrated biological tissues. In cartilage mechanics, this type of mixture, where the fluid and solid constituents are both assumed to be intrinsically incompressible, is often called a biphasic material. Various physiological processes involve the interaction of a viscous fluid with a porous-hydrated tissue, as encountered in synovial joint lubrication, cardiovascular mechanics, and respiratory mechanics. The objective of this study was to implement a finite element solver in the open-source software febio that models dynamic interactions between a viscous fluid and a biphasic domain, accommodating finite deformations of both domains as well as fluid exchanges between them. For compatibility with our recent implementation of solvers for computational fluid dynamics (CFD) and fluid-structure interactions (FSI), where the fluid is slightly compressible, this study employs a novel hybrid biphasic formulation where the porous skeleton is intrinsically incompressible but the fluid is also slightly compressible. The resulting biphasic-FSI (BFSI) implementation is verified against published analytical and numerical benchmark problems, as well as novel analytical solutions derived for the purposes of this study. An illustration of this BFSI solver is presented for two-dimensional (2D) airflow through a simulated face mask under five cycles of breathing, showing that masks significantly reduce air dispersion compared to the no-mask control analysis. In addition, we model three-dimensional (3D) blood flow in a bifurcated carotid artery assuming porous arterial walls and verify that mass is conserved across all fluid-permeable boundaries. The successful formulation and implementation of this BFSI solver offers enhanced multiphysics modeling capabilities that are accessible via an open-source software platform.

Tribological Modeling of the Hip Joint

AbstractThe paper presents a series of aspects regarding the main biotribological phenomena occurring in the synovial joints. Although a great deal of research is carried out around the world about the biotribological processes in the human body's synovial joints, due to their complexity, they are not yet been fully understood and cannot establish a unique model of lubrication mechanism in these joints. The problem is complicated by the fact that in reality the cartilage is neither homogeneous nor isotropic and undergoes a large deformation during loading. According to several researchers, implantation and expulsion of synovial fluid in cartilage is not a simple phenomenon, although the boosted or weeping type of lubrication suggests this. The self‐generating lubrication mechanism postulated by Mow et al. (1987) takes into account the biphasic nature of cartilage and is based on the load‐dividing factor between the solid phase and the liquid. In recent years, studies have also been carried out to explore possible links between synovial joint lubrication mechanisms and degeneration processes. Tribological modeling is based on a number of parameters, such as: lubricant film thickness (or synovial fluid), maximum physiological load, articular cartilage surface roughness, friction coefficient, surface roughness, and lubrication regime.

A porohyperelastic lubrication model for articular cartilage in the natural synovial joint

This work focuses on the proposed mechanisms for the lubrication of synovial joints and applies them to an idealised bearing geometry considering a porohyperelastic material (cartilage) rotating against a stationary rigid impermeable surface. The model captures the behaviour of all lubrication regimes including fluid film formation and boundary contact as the load capacity is increased, representing a major advancement in modelling cartilage mechanics. Transient responses in the fluid phase are shown to be faster than those in the solid phase with the former decaying over time as fluid is exuded from the material. The complex behaviour of fluid migrating to and from the lubricating film is captured which leads to a better understanding of the hydration and friction mechanisms observed.

The Effect of Dexamethasone, Adrenergic and Cholinergic Receptor Agonists on Phospholipid Metabolism in Human Osteoarthritic Synoviocytes.

Phospholipids (PLs) possess the unique ability to contribute to synovial joint lubrication. The aim of our study was to determine for the first time the effect of dexamethasone and some adrenergic and cholinergic agonists on the biosynthesis and release of PLs from human fibroblast-like synoviocytes (FLS). Osteoarthritic human knee FLS were treated with dexamethasone, terbutaline, epinephrine, carbachol, and pilocarpine, or the glucocorticoid receptor antagonist RU 486. Simultaneously PL biosynthesis was determined through the incorporation of stable isotope-labeled precursors into PLs. Radioactive isotope-labeled precursors were used to radiolabel PLs for the subsequent quantification of their release into nutrient media. Lipids were extracted and quantified using electrospray ionization tandem mass spectrometry or liquid scintillation counting. Dexamethasone significantly decreased the biosynthesis of phosphatidylcholine, phosphatidylethanolamine (PE), PE-based plasmalogen, and sphingomyelin. The addition of RU 486 abolished these effects. A release of PLs from FLS into nutrient media was not recognized by any of the tested agents. None of the adrenergic or cholinergic receptor agonists modulated the PL biosynthesis. We demonstrate for the first time an inhibitory effect of dexamethasone on the PL biosynthesis of FLS from human knees. Moreover, our study indicates that the PL metabolism of synovial joints and lungs are differently regulated.

Repulsive surfaces and lamellar lubrication of synovial joints

Surface-active phospholipid (SAPL) secreted in the synovial joint plays an important role in cartilage integrity. In healthy joints, phospholipid multibilayers coat the cartilage surface, providing boundary lamellar-repulsive hydration lubrication. Current mechanism for lubrication of synovial joints, as well as the physical and chemical nature of the cartilage surface is discussed. Friction between phospholipid (PL) bilayers attached to cartilage surfaces is considered including a discussion on the recent observation of an extreme friction reduction as a consequence of a less charged hydrophilic cartilage surface. It is proposed that the highly efficient lubrication occurring in natural joints arises from the presence of negatively charged cartilage surfaces. The lamellar-repulsive mechanisms for the reduction of friction is supported by phospholipid lamellar phases and charged macromolecules residing between contacting cartilage surfaces at pH ∼7.4.

Hierarchical excluded volume screening in solutions of bottlebrush polymers.

Polymer bottlebrushes provide intriguing features being relevant both in nature and in synthetic systems. While their presence in the articular cartilage optimizes synovial joint lubrication, bottlebrushes offer pathways for fascinating applications, such as within super-soft elastomers or for drug delivery. However, the current theoretical understanding lacks completeness, primarily due to the complicated interplay of many length scales. Herein, we develop an analytical model that demonstrates how structural properties of bottlebrushes depend on the concentration, ranging from dilute solutions to highly concentrated melts. The validity of our model is supported by data from extensive molecular dynamics simulations. We demonstrate that the hierarchical structure of bottlebrushes dictates a sequence of conformational changes as the solution concentration increases. The effect is mediated by screening of excluded volume interactions at subsequent structural parts of the bottlebrushes. Our findings provide important insights that should enable improved customization of novel materials based on the architectural design of polymer bottlebrushes.

Lubrication synergy: Mixture of hyaluronan and dipalmitoylphosphatidylcholine (DPPC) vesicles

Phospholipids and hyaluronan have been implied to fulfil important roles in synovial joint lubrication. Since both components are present in synovial fluid, self-assembly structures formed by them should also be present. We demonstrate by small angle X-ray scattering that hyaluronan associates with the outer shell of dipalmitoylphophatidylcholine (DPPC) vesicles in bulk solution. Further, we follow adsorption to silica from mixed hyaluronan/DPPC vesicle solution by Quartz Crystal Microbalance with Dissipation measurements. Atomic Force Microscope imaging visualises the adsorbed layer structure consisting of non-homogeneous phospholipid bilayer with hyaluronan/DPPC aggregates on top. The presence of these aggregates generates a long-range repulsive surface force as two such surfaces are brought together. However, the aggregates are easily deformed, partly rearranged into multilayer structures and partly removed from between the surfaces under high loads. These layers offer very low friction coefficient (<0.01), high load bearing capacity (≈23MPa), and self-healing ability. Surface bound DPPC/hyaluronan aggregates provide a means for accumulation of lubricating DPPC molecules on sliding surfaces.

Polymer-brush lubrication: a review of recent theoretical advances.

This review compiles recent theoretical advances to describe compressive and shear forces of polymer-brush bilayers, which consist of two opposing brushes in contact. Such model systems for polymer-brush lubrication are frequently used as a benchmark to gain insight into biological problems, e.g., synovial joint lubrication. Based on scaling theory, I derive conformational and collective properties of polymer-brush bilayers in equilibrium and out-of-equilibrium situations, such as shear forces in the linear and nonlinear response regimes of stationary shear and under non-stationary shear. Furthermore, I discuss the influence of macromolecular inclusions and electrostatic interactions on polymer-brush lubrication. Comparisons to alternative analytical approaches, experiments and numerical results are performed. Special emphasis is given to methods for simulating polymer-brush bilayers using molecular dynamics simulations.

Supramolecular synergy in the boundary lubrication of synovial joints.

Hyaluronan, lubricin and phospholipids, molecules ubiquitous in synovial joints, such as hips and knees, have separately been invoked as the lubricants responsible for the remarkable lubrication of articular cartilage; but alone, these molecules cannot explain the extremely low friction at the high pressures of such joints. We find that surface-anchored hyaluronan molecules complex synergistically with phosphatidylcholine lipids present in joints to form a boundary lubricating layer, which, with coefficient of friction μ≈0.001 at pressures to over 100 atm, has a frictional behaviour resembling that of articular cartilage in the major joints. Our findings point to a scenario where each of the molecules has a different role but must act together with the others: hyaluronan, anchored at the outer surface of articular cartilage by lubricin molecules, complexes with joint phosphatidylcholines to provide the extreme lubrication of synovial joints via the hydration–lubrication mechanism.

The nonlinear viscoelasticity of hyaluronic acid and its role in joint lubrication.

Hyaluronic acid solutions have been widely studied due to their relevance to the rheological behavior of synovial fluid and joint lubrication. Ambulatory joint motion is typically large oscillatory deflections; therefore, large amplitude oscillatory shear strain experiments are used to examine the relevant non-linear viscoelastic properties of these solutions. Using the sequence of physical processes method to analyze data provides time dependent viscoelastic moduli, which exhibit a clear physiologically relevant behavior to hyaluronic acids non-linear viscoelasticity. In particular, it is seen that during peak strain/acceleration, the time dependent elastic modulus peaks and the loss modulus is at a minimum. The hyaluronic acid can provide an immediate elastic response to sudden forces, acting like a shock absorber during sudden changes in direction of motion or maximum deflection. However, during peak rate, the elastic modulus is at a minimum and the loss modulus is at a maximum, which provides greater efficacy to hydrodynamic shear lubrication.

Lubricin is Required for the Structural Integrity and Post-natal Maintenance of TMJ

The Proteoglycan 4 (Prg4) product lubricin plays essential roles in boundary lubrication and movement in limb synovial joints, but its roles in temporomandibular joint (TMJ) are unclear. Thus, we characterized the TMJ phenotype in wild-type and Prg4–/– mouse littermates over age. As early as 2 weeks of age, mutant mice exhibited hyperplasia in the glenoid fossa articular cartilage, articular disc, and synovial membrane. By 1 month of age, there were fewer condylar superficial tenascin-C/Col1-positive cells and more numerous apoptotic condylar apical cells, while chondroprogenitors displayed higher mitotic activity, and Sox9-, Col2-, and ColX-expressing chondrocyte zones were significantly expanded. Mutant subchondral bone contained numerous Catepsin K- expressing osteoclasts at the chondro-osseous junction, increased invasive marrow cavities, and suboptimal subchondral bone. Mutant glenoid fossa, disc, synovial cells, and condyles displayed higher Hyaluronan synthase 2 expression. Mutant discs also lost their characteristic concave shape, exhibited ectopic chondrocyte differentiation, and occasionally adhered to condylar surfaces. A fibrinoid substance of unclear origin often covered the condylar surface. By 6 months of age, mutant condyles displayed osteoarthritic degradation with apical/mid-zone separation. In sum, lubricin exerts multiple essential direct and indirect roles to preserve TMJ structural and cellular integrity over post-natal life.