Cartilage-on-cartilage contact: effect of compressive loading on tissue deformations and structural integrity of bovine articular cartilage.

OBJECTIVE: This study aims to characterize the deformations in articular cartilage under compressive loading and link these to changes in the extracellular matrix constituents described by magnetic resonance imaging (MRI) relaxation times in an experimental model mimicking in vivo cartilage-on-cartilage contact. DESIGN: Quantitative MRI images, T1, T2 and T1ρ relaxation times, were acquired at 9.4T from bovine femoral osteochondral explants before and immediately after loading. Two-dimensional intra-tissue displacement and strain fields under cyclic compressive loading (350N) were measured using the displacement encoding with stimulated echoes (DENSE) method. Changes in relaxation times in response to loading were evaluated against the deformation fields. RESULTS: Deformation fields showed consistent patterns among all specimens, with maximal strains at the articular surface that decrease with tissue depth. Axial and transverse strains were maximal around the center of the contact region, whereas shear strains were minimal around the contact center but increased towards contact edges. A decrease in T2 and T1ρ was observed immediately after loading whereas the opposite was observed for T1. No correlations between cartilage deformation patterns and changes in relaxation times were observed. CONCLUSIONS: Displacement encoding combined with relaxometry by MRI can noninvasively monitor the cartilage biomechanical and biochemical properties associated with loading. The deformation fields reveal complex patterns reflecting the depth-dependent mechanical properties, but intra-tissue deformation under compressive loading does not correlate with structural and compositional changes. The compacting effect of cyclic compression on the cartilage tissue was revealed by the change in relaxation time immediately after loading.

Functional assessment of strains around a full-thickness and critical sized articular cartilage defect under compressive loading using MRI.

OBJECTIVE: The objective of this study was to evaluate the effect of full-thickness chondral defects on intratissue deformation patterns and matrix constituents in an experimental model mimicking in vivo cartilage-on-cartilage contact conditions. DESIGN: Pairs of bovine osteochondral explants, in a unique cartilage-on-cartilage model system, were compressed uniaxially by 350 N during 2 s loading and 1.4 s unloading cycles (≈1700 repetitions). Tissue deformations under quasi-steady state load deformation response were measured with displacement encoded imaging with stimulated echoes (DENSE) in a 9.4 T magnetic resonance imaging (MRI) scanner. Pre- and post-loading, T1, T2 and T1ρ relaxation time maps were measured. We analyzed differences in strain patterns and relaxation times between intact cartilage (n = 8) and cartilage in which a full-thickness and critical sized defect was created (n = 8). RESULTS: Under compressive loading, strain magnitudes were elevated at the defect rim, with elevated tensile and compressive principal strains (Δϵmax = 4.2%, P = 0.02; Δϵmin = -4.3%, P = 0.02) and maximum shear strain at the defect rim (Δγmax = 4.4%, P = 0.007). The opposing cartilage showed minimal increase in strain patterns at contact with the defect rim but decreased strains opposing the defect. After defect creation, T1, T2 and T1ρ relaxation times were elevated at the defect rim only. Following loading, the overall relaxations times of the defect tissue and especially at the rim, increased compared to intact cartilage. CONCLUSIONS: This study demonstrates that the local biomechanical changes occurring after defect creation may induce tissue damage by increasing shear strains and depletion of cartilage constituents at the defect rim under compressive loading.

Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage.

OBJECTIVE: Articular cartilage defects commonly result from traumatic injury and predispose to degenerative joint diseases. To test the hypothesis that aberrant healing responses and chronic inflammation lead to osteoarthritis (OA), we examined spatiotemporal changes in joint tissues after cartilage injury in murine knees. Since intra-articular injection of hyaluronan (HA) can attenuate injury-induced osteoarthritis in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1(-/-)). DESIGN: Femoral groove cartilage of WT and Has1(-/-) mice was debrided to generate a non-bleeding wound. Macroscopic imaging, histology, and gene expression were used to evaluate naïve, sham-operated, and injured joints. RESULTS: Acute responses (1-2 weeks) in injured joints from WT mice included synovial hyperplasia with HA deposition and joint-wide increases in expression of genes associated with inflammation, fibrosis, and extracellular matrix (ECM) production. By 4 weeks, some resurfacing of damaged cartilage occurred, and early cell responses were normalized. Cartilage damage in Has1(-/-) mice also induced early responses; however, at 4 weeks, inflammation and fibrosis genes remained elevated with widespread cartilage degeneration and fibrotic scarring in the synovium and joint capsule. CONCLUSIONS: We conclude that the ineffective repair of injured cartilage in Has1(-/-) joints can be at least partly explained by the markedly enhanced expression of particular genes in pathways linked to ECM turnover, IL-17/IL-6 cytokine signaling, and apoptosis. Notably, Has1 ablation does not alter gross HA content in the ECM, suggesting that HAS1 has a unique function in the metabolism of inflammatory HA matrices.

Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis.

A major objective of this article is to examine the research implications of recently available genome-wide expression profiles of cartilage from human osteoarthritis (OA) joints. We propose that, when viewed in the light of extensive earlier work, this novel data provides a unique opportunity to reorient the design of experimental systems toward clinical relevance. Specifically, in the area of cartilage explant biology, this will require a fresh evaluation of existing paradigms, so as to optimize the choices of tissue source, cytokine/growth factor/nutrient addition, and biomechanical environment for discovery. Within this context, we firstly discuss the literature on the nature and role of potential catabolic mediators in OA pathology, including data from human OA cartilage, animal models of OA, and ex vivo studies. Secondly, due to the number and breadth of studies on IL-1ß in this area, a major focus of the article is a critical analysis of the design and interpretation of cartilage studies where IL-1ß has been used as a model cytokine. Thirdly, the article provides a data-driven perspective (including genome-wide analysis of clinical samples, studies on mutant mice, and clinical trials), which concludes that IL-1ß should be replaced by soluble mediators such as IL-17 or TGF-ß1, which are much more likely to mimic the disease in OA model systems. We also discuss the evidence that changes in early OA can be attributed to the activity of such soluble mediators, whereas late-stage disease results more from a chronic biomechanical effect on the matrix and cells of the remaining cartilage and on other local mediator-secreting cells. Lastly, an updated protocol for in vitro studies with cartilage explants and chondrocytes (including the use of specific gene expression arrays) is provided to motivate more disease-relevant studies on the interplay of cytokines, growth factors, and biomechanics on cellular behavior.

Mechanostasis in apoptosis and medicine.

Mechanostasis describes a complex and dynamic process where cells maintain equilibrium in response to mechanical forces. Normal physiological loading modes and magnitudes contribute to cell proliferation, tissue growth, differentiation and development. However, cell responses to abnormal forces include compensatory apoptotic mechanisms that may contribute to the development of tissue disease and pathological conditions. Mechanotransduction mechanisms tightly regulate the cell response through discrete signaling pathways. Here, we provide an overview of links between pro- and anti-apoptotic signaling and mechanotransduction signaling pathways, and identify potential clinical applications for treatments of disease by exploiting mechanically-linked apoptotic pathways.

In situ deformation of cartilage in cyclically loaded tibiofemoral joints by displacement-encoded MRI.

OBJECTIVES: Cartilage displacement and strain patterns were documented noninvasively in intact tibiofemoral joints in situ by magnetic resonance imaging (MRI). This study determined the number of compressive loading cycles required to precondition intact joints prior to imaging, the spatial distribution of displacements and strains in cartilage using displacement-encoded MRI, and the depth-dependency of these measures across specimens. DESIGN: Juvenile porcine tibiofemoral joints were cyclically compressed at one and two times body weight at 0.1 Hz to achieve a quasi-steady state load-displacement response. A 7.0 T MRI scanner was used for displacement-encoded imaging with stimulated echoes and a fast spin echo acquisition (DENSE-FSE) in eight intact joints. Two-dimensional displacements and strains were determined throughout the thickness of the tibial and femoral cartilage and then normalized over the tissue thickness. RESULTS: Two-dimensional displacements and strains were heterogeneous through the depth of femoral and tibial cartilage under cyclic compression. Strains in the loading direction were compressive and were maximal in the middle zone of femoral and tibial cartilage, and tensile strains were observed in the direction transverse to loading. CONCLUSIONS: This study determined the depth-dependent displacements and strains in intact juvenile porcine tibiofemoral joints using displacement-encoded imaging. Displacement and strain distributions reflect the heterogeneous biochemistry of cartilage and the biomechanical response of the tissue to compression in the loading environment of an intact joint. This unique information about the biomechanics of cartilage has potential for comparisons of healthy and degenerated tissue and in the design of engineered replacement tissues.

Modified endoscopic dacryocystorhinostomy with posterior lacrimal sac flap for nasolacrimal duct obstruction.

OBJECTIVES: To evaluate a new technique of modified endoscopic dacryocystorhinostomy involving the creation of a large posterior flap at the lacrimal sac and to compare its success rate with that of the conventional endoscopic method of excising the entire medial lacrimal sac wall as a surgical treatment for epiphora caused by nasolacrimal duct obstruction. DESIGN: Retrospective, interventional, and comparative case series. SETTING: University teaching hospital, Hong Kong. PATIENTS AND METHODS: Only adults with primary nasolacrimal duct obstruction were included. Consecutive endoscopic dacryocystorhinostomy was performed using two different techniques from July 1999 to June 2001. The new technique involved the creation of a large posterior flap at the medial lacrimal sac wall, reflecting it posteriorly, followed by removal of the remaining small anterior flap (the LSF group). Other patients had the entire medial lacrimal sac wall excised (the ELS group). MAIN OUTCOME MEASURES: Surgical success was defined by free fluorescein drainage from the conjunctival sac into the rhinostomy site at least 3 months after silicone stent removal. RESULTS: Ninety-nine procedures were performed in 99 patients. The success rate was 89.1% (41/46) in the LSF group and 71.7% (38/53) in the ELS group. The difference between the two groups was statistically significant (Chi squared test, P=0.031). CONCLUSIONS: Our new and modified technique of endonasal dacryocystorhinostomy has a greater success rate than conventional endonasal dacryocystorhinostomy. A large-scale prospective randomised controlled trial to further evaluate the efficacy and safety of this surgical technique is under way.