Decision letter for "Lubricin Contributes to Homeostasis of Articular Cartilage by Modulating Differentiation of Superficial Zone Cells"

Abstract Articular cartilage is a highly nonhomogeneous, anisotropic and multiphase biomaterial consisting of mainly collagen fibrils, proteoglycans and water. Noncalcified cartilage is morphologically divided into three zones along the depth, i.e. superficial, transitional and radial zones. The thickness, density and alignment of collagen fibrils vary from the superficial zone, where fibrils are oriented parallel to the articular surface, to the radial zone where fibrils are perpendicular to the boundary between bone, and cartilage. The concentration of proteoglycans increases with the depth from the cartilage surface. These regional differences have significant implications to the mechanical function of joints, which is to be explored theoretically in the present work by considering inhomogeneity along the cartilage depth. A nonlinear fibril reinforced poroelastic model is employed as per Li et al. (1999) in which the collagen fibrils were modeled as a distinct constituent whose tensile stiffness was taken to be very high and be strain dependent but whose compressive stiffness was neglected.

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Inflammatory Response of Articular Cartilage to Femoroacetabular Impingement in the Hip

The American Journal of Sports Medicine ◽

10.1177/0363546520918804 ◽

2020 ◽

Vol 48 (7) ◽

pp. 1647-1656 ◽

Cited By ~ 2

Author(s):

Masahiko Haneda ◽

Muhammad Farooq Rai ◽

Regis J. O’Keefe ◽

Robert H. Brophy ◽

John C. Clohisy ◽

...

Keyword(s):

Articular Cartilage ◽

Femoroacetabular Impingement ◽

Inflammatory Markers ◽

Type Ii Collagen ◽

Developmental Dysplasia ◽

Control Group ◽

Etiologic Factor ◽

Superficial Zone ◽

Average Percentage ◽

Impingement Zone

Background: Femoroacetabular impingement (FAI) has been proposed as an etiologic factor in up to 50% of hips with osteoarthritis (OA). Inflammation is thought to be one of the main initiators of OA, yet little is known about the origin of intra-articular inflammation in FAI hips. Hypothesis: Articular cartilage from the impingement zone of patients with FAI has high levels of inflammation, reflecting initial inflammatory process in the hip. Study Design: Controlled laboratory study. Methods: Head-neck cartilage samples were obtained from patients with cam FAI (cam FAI, early FAI; n = 15), advanced OA secondary to cam FAI (FAI OA, late FAI; n = 15), and advanced OA secondary to developmental dysplasia of the hip (DDH OA, no impingement; n = 15). Cartilage procured from young adult donors (n = 7) served as control. Safranin O–stained sections were assessed for cartilage abnormality. Tissue viability was detected by TUNEL assay. Immunostaining of interleukin 1β (IL-1β), catabolic markers (matrix metalloproteinase 13 [MMP-13], a disintegrin and metalloproteinase with thrombospondin motif 4 [ADAMTS-4], aggrecan antibody to C-terminal neoepitope [NITEGE]), and an anabolic marker (type II collagen [COL2]) was performed to evaluate molecular inflammation and metabolic activity. The average percentage of immunopositive cells from the total cell count was calculated. Kruskal-Wallis test followed by Steel-Dwass post hoc test was used for multiple comparisons. Results: Microscopic osteoarthritic changes were more prevalent in cartilage of cam FAI and FAI OA groups compared with DDH OA and control groups. Cartilage in cam FAI and FAI OA groups, versus the DDH group, had higher expression of inflammatory molecules IL-1β (69.7% ± 18.1% and 72.5% ± 13.2% vs 32.7% ± 14.4%, respectively), MMP-13 (79.6% ± 12.6% and 71.4% ± 18.8% vs 38. 5% ± 13.3%), ADAMTS-4 (83.9% ± 12.2% and 82.6% ± 12.5% vs 45.7% ± 15.5%), and COL2 (93.6% ± 3.9% and 92.5% ± 5.8% vs 53.3% ± 21.0%) ( P < .001). Expression of NITEGE was similar among groups (cam FAI, 89.7% ± 7.7%; FAI OA, 95.7% ± 4.7%; DDH OA, 93.9% ± 5.2%; P = .0742). The control group had minimal expression of inflammatory markers. Inflammatory markers were expressed in all cartilage zones of early and late FAI but only in the superficial zone of the no impingement group. Conclusion: Cartilage from the impingement zone in FAI is associated with a high expression of inflammatory markers, extending throughout all cartilage zones. Clinical Relevance: Inflammation associated with FAI likely has a deleterious effect on joint homeostasis. Further clinical and translational studies are warranted to assess whether and how surgical treatment of FAI reduces molecular inflammation.

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Wnt/β-catenin signaling contributes to articular cartilage homeostasis through lubricin induction in the superficial zone

Arthritis Research & Therapy ◽

10.1186/s13075-019-2041-5 ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 6

Author(s):

Fengjun Xuan ◽

Fumiko Yano ◽

Daisuke Mori ◽

Ryota Chijimatsu ◽

Yuji Maenohara ◽

...

Keyword(s):

Articular Cartilage ◽

Mechanical Loading ◽

Cartilage Degeneration ◽

Mrna Levels ◽

Superficial Zone ◽

Gain Of Function ◽

Wnt Ligands ◽

Signaling Activation ◽

Signaling Activity

Abstract Background Both loss- and gain-of-function of Wnt/β-catenin signaling in chondrocytes result in exacerbation of osteoarthritis (OA). Here, we examined the activity and roles of Wnt/β-catenin signaling in the superficial zone (SFZ) of articular cartilage. Methods Wnt/β-catenin signaling activity was analyzed using TOPGAL mice. We generated Prg4-CreERT2;Ctnnb1fl/fl and Prg4-CreERT2;Ctnnb1-ex3fl/wt mice for loss- and gain-of-function, respectively, of Wnt/β-catenin signaling in the SFZ. Regulation of Prg4 expression by Wnt/β-catenin signaling was examined in vitro, as were upstream and downstream factors of Wnt/β-catenin signaling in SFZ cells. Results Wnt/β-catenin signaling activity, as determined by the TOPGAL reporter, was high specifically in the SFZ of mouse adult articular cartilage, where Prg4 is abundantly expressed. In SFZ-specific β-catenin-knockout mice, OA development was significantly accelerated, which was accompanied by decreased Prg4 expression and SFZ destruction. In contrast, Prg4 expression was enhanced and cartilage degeneration was suppressed in SFZ-specific β-catenin-stabilized mice. In primary SFZ cells, Prg4 expression was downregulated by β-catenin knockout, while it was upregulated by β-catenin stabilization by exon 3 deletion or treatment with CHIR99021. Among Wnt ligands, Wnt5a, Wnt5b, and Wnt9a were highly expressed in SFZ cells, and recombinant human WNT5A and WNT5B stimulated Prg4 expression. Mechanical loading upregulated expression of these ligands and further promoted Prg4 transcription. Moreover, mechanical loading and Wnt/β-catenin signaling activation increased mRNA levels of Creb1, a potent transcription factor for Prg4. Conclusions We demonstrated that Wnt/β-catenin signaling regulates Prg4 expression in the SFZ of mouse adult articular cartilage, which plays essential roles in the homeostasis of articular cartilage.

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Removal of the superficial zone of bovine articular cartilage does not increase its frictional coefficient

Osteoarthritis and Cartilage ◽

10.1016/j.joca.2004.08.009 ◽

2004 ◽

Vol 12 (12) ◽

pp. 947-955 ◽

Cited By ~ 42

Author(s):

R. Krishnan ◽

M. Caligaris ◽

R.L. Mauck ◽

C.T. Hung ◽

K.D. Costa ◽

...

Keyword(s):

Articular Cartilage ◽

Frictional Coefficient ◽

Superficial Zone ◽

Bovine Articular Cartilage

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A Novel Proteoglycan Synthesized and Secreted by Chondrocytes of the Superficial Zone of Articular Cartilage

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.1994.1219 ◽

1994 ◽

Vol 311 (1) ◽

pp. 144-152 ◽

Cited By ~ 256

Author(s):

B.L. Schumacher ◽

J.A. Block ◽

T.M. Schmid ◽

M.B. Aydelotte ◽

K.E. Kuettner

Keyword(s):

Articular Cartilage ◽

Superficial Zone

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