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Farshid Guilak

Publications and source records attributed to Farshid Guilak.

65 records · Page 4Linked to original sources
PubMed2002

Chondropathy after meniscal tear or partial meniscectomy in a canine model.

A primary goal in considering treatment for meniscal injuries is the preservation of the health of the articular cartilage. However, the chondroprotective effects of various techniques for meniscal injury treatments are unknown. We used a canine model to quantify articular cartilage degeneration in the medial compartment of the canine knee, resulting from a surgically created tear or a partial meniscectomy (PM) of the posterior region of the medial meniscus (each group, n = 10). After sacrifice at 12 weeks, the development of gross chondropathy and the changes in cartilage tensile stiffness were quantified, and correlations between these measurements were examined. Both treatment surgical treatment groups caused significantly greater gross chondropathy as compared to the unoperated contralateral controls. Cartilage tensile stiffness was significantly lower than unoperated controls by nearly 28% in both experimental groups. However, there were no significant differences observed between the gross chondropathy or the cartilage mechanical property changes between the experimental groups. Importantly, the severity of gross chondropathy was found to significantly correlate with the decrement in tensile stiffness properties of the articular cartilage. These findings indicate that significant degeneration of canine articular cartilage develops to a similar degree in the presence of a partially healed meniscus tear or a PM of the knee.

Animals↗
PubMed2002

Observations on the growth of loose bodies in joints.

The categorization, origin, natural history, and histopathology of loose bodies in joints are well described in the literature. Clinical and basic science data have indirectly concluded that loose bodies grow over time; however, to date, there is no clearly documented published clinical example. This case report demonstrates the dramatic enlargement of 2 osteochondral loose bodies in a patient's knee over the course of a decade. The loose bodies possess a large number of viable cells; and growth appears to have occurred through encapsulation of the niduses by multiple layers of fibrocartilagenous tissue, thus confirming the findings of earlier studies.

Adult↗
PubMed2002

The mechanical properties of the human hip capsule ligaments.

The human hip capsule is adapted to facilitate upright posture, joint stability, and ambulation, yet it routinely is excised in hip surgery without a full understanding of its mechanical contributions. The objective of this study was to provide information about the mechanical properties of the ligaments that form the hip capsule. Cadaver bone-ligament-bone specimens of the iliofemoral, ischiofemoral, and femoral arcuate ligaments were tested to failure in tension. The hip capsule was found to be an inhomogeneous structure and should be recognized as being composed of discrete constituent ligaments. The anterior ligaments, consisting of the 2 arms of the iliofemoral ligament, were much stronger than the posterior ischiofemoral ligament, withstanding greater force at failure and exhibiting greater stiffness. Knowledge of the anatomy and mechanical properties of the capsule may help the hip surgeon choose an appropriate surgical approach or repair strategy.

Aged↗
PubMed2002

An axisymmetric boundary integral model for assessing elastic cell properties in the micropipette aspiration contact problem.

The micropipette aspiration technique has been used extensively in recent years to measure the mechanical properties of living cells. In the present study, a boundary integral formulation with quadratic elements is used to predict the elastic equilibrium response in the micropipette aspiration contact problem for a three-dimensional incompressible spherical continuum cell model (Young's modulus E). In contrast to the halfspace model, the spherical cell model accounts for nonlinearities in the cell response which result from a consideration of geometric factors including the finite cell dimension (radius R), curvature of the cell boundary, evolution of the cell-micropipette contact region and curvature of the edges of the micropipette (inner radius a, edge curvature radius epsilon). The efficiency of the boundary element method facilitates the quantification of cell response as a function of the scaled pressure p/E, for the range of parameters a/R = 0.4-0.7, epsilon/a = 0.02-0.08, in terms of two measures that can be quantified using video microscopy. These are the aspiration length, which measures projection of the cell into the micropipette, and a characteristic strain, which measures stretching along the symmetry axis. For both measures of cell response, the resistance to aspiration is found to decrease with increasing values of the aspect ratio a/R and curvature parameter epsilon/a, and the nonlinearities in the cell response are most pronounced in the earlier portion of the aspiration test. The aspiration length is found to exhibit less sensitivity to the aspect ratio a/R than to the curvature parameter epsilon/a, whereas the characteristic strain, which provides a more realistic measure of overall cell stiffness, exhibits sensitivity to the aspect ratio a/R. The resistance to aspiration in the spherical cell model is initially less than that of the half space model but eventually exceeds the halfspace prediction and the deviation between the two models increases as the parameter epsilon/a decreases. Adjustment factors for the Young's modulus E, as predicted by the halfspace model, are presented and the deviation from the spherical cell model is found to be as large as 35%, when measured locally on the response curve. In practice, the deviation will be less than the maximum figure but its precise value will depend on the number of data points available in the experiment and the specific curve-fitting procedure. The spherical cell model allows for efficient and more realistic simulations of the micropipette aspiration contact problem and quantifies two observable measures of cell response that, using video microscopy, can facilitate the determination of Young's modulus for various cell populations while, simultaneously, providing a means of evaluating the validity of continuum cell models. Furthermore, this numerical model may be readily extended to account for more complex geometries, inhomogeneities in cellular properties, or more complex constitutive descriptions of the cell.

Cell Adhesion↗
PubMed2002

Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts.

G protein-coupled receptors (GPCRs) play a key role in regulating bone remodeling. Whether GPCRs exert anabolic or catabolic osseous effects may be determined by the rate of receptor desensitization in osteoblasts. Receptor desensitization is largely mediated by direct phosphorylation of GPCR proteins by a family of enzymes termed GPCR kinases (GRKs). We have selectively manipulated GRK activity in osteoblasts in vitro and in vivo by overexpressing a GRK inhibitor. We found that expression of a GRK inhibitor enhanced parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor-stimulated cAMP generation and inhibited agonist-induced phosphorylation of this receptor in cell culture systems, consistent with attenuation of receptor desensitization. To determine the effect of GRK inhibition on bone formation in vivo, we targeted the expression of a GRK inhibitor to mature osteoblasts using the mouse osteocalcin gene 2 (OG2) promoter. Transgenic mice demonstrated enhanced bone remodeling as well as enhanced urinary excretion of the osteoclastic activity marker dexoypyridinoline. Both osteoprotegrin and OPG ligand mRNA levels were altered in calvaria of transgenic mice in a pattern that would promote osteoclast activation. The predominant effect of the transgene, however, was anabolic, as evidenced by an increase in bone density and trabecular bone volume in the transgenic mice compared with nontransgenic littermate controls.

Animals↗
PubMed2001

Joint degeneration following meniscal allograft transplantation in a canine model: mechanical properties and semiquantitative histology of articular cartilage.

This study examined the hypothesis that meniscal allograft transplantation serves a "chondroprotective" role and prevents the histological and biomechanical changes of the articular cartilage following meniscectomy. Skeletally mature mongrel dogs underwent total medial meniscectomy and received either a fresh meniscal allograft ( n=10) or no further treatment ( n=10). Semiquantitative histology and biomechanical analysis of the femoral articular cartilage was used to assess cartilage pathology 12 weeks following surgery. Histological analysis showed significant changes in cartilage structure that did not differ between the meniscectomy and allograft transplantation groups. Similarly, the tensile modulus of the surface zone cartilage was significantly lower than that in unoperated controls following either meniscectomy or allograft transplantation. A significant correlation was observed between the biomechanical and histological changes, suggesting that degenerative changes in cartilage structure and mechanical function are interrelated. Our findings do not support the hypothesis that meniscal allograft transplantation provides chondroprotection of the femoral condyle and also suggest that it does not lead to increased degenerative changes.

Animals↗
PubMedDate not supplied

The development of posttraumatic arthritis after articular fracture.

Posttraumatic arthritis (PTA) is one of the most frequent causes of disability after trauma involving weight-bearing joints and is estimated to be responsible for approximately 10% of the 21 million Americans who have osteoarthritis. Despite a number of similarities in the pathology and end-stage disease of PTA with primary osteoarthritis, the mechanisms involved in the onset and progression of joint degeneration after articular fracture are poorly understood. The largest area of study regarding articular fractures and the development of arthritic changes has focused on the role of adequate surgical reduction of the articular surfaces. However, it is now apparent that a number of complex and interacting biomechanical, biochemical, and, possibly, genetic factors contribute to the development of osteoarthritic changes in the joint after joint trauma, ranging from the cell and molecular level to the joint and systemic level. In this paper, we discuss the potential roles of the initial impact and fracture as well as the subsequent alterations in joint loading, biomechanical and metabolic properties of the cartilage, local and systemic inflammatory cytokines, and viability of chondrocytes in the progression of PTA. An improved understanding of the mechanisms involved in the development of PTA will hopefully lead to the improvement of surgical and nonsurgical therapies for this disease.

Arthritis↗
PubMedDate not supplied

Site-specific molecular diffusion in articular cartilage measured using fluorescence recovery after photobleaching.

Diffusive transport of solutes is critical to the normal function of articular cartilage. The diffusion of macromolecules through cartilage may be affected by the local composition and structure, which vary with depth from the tissue surface. We hypothesized that the diffusion coefficient of uncharged molecules also varies with depth and molecular size. We used fluorescence recovery after photobleaching (FRAP) to measure site-specific diffusion coefficients of fluorescent dextran molecules (3, 40, 70, and 500 kDa) in porcine articular cartilage. The diffusion coefficients measured using FRAP exhibited an inverse size dependence and were in general agreement with those measured using other techniques. The diffusion coefficients for all molecules varied significantly with depth in a manner that depended upon the size of the diffusing molecule. The diffusion coefficients for the 3 and 500 kDa dextrans were 1.6 and 2.4 times greater, respectively, in the surface zone as compared to the middle and deep zones, whereas the diffusion coefficients of the 40 and 70 kDa dextrans were 0.3 and 0.2 times lower in the surface zone as compared to the middle and deep zones. These differences may reflect variations in the structure and composition of collagen, proteoglycans, and other macromolecules among the zones.

Animals↗