Developmental and osteoarthritic changes in Col6a1-knockout mice: Biomechanics of type VI collagen in the cartilage pericellular matrix

Alexopoulos, LG; Youn, I; Bonaldo, P; Guilak, F

dc.contributor.author	Alexopoulos, LG	en
dc.contributor.author	Youn, I	en
dc.contributor.author	Bonaldo, P	en
dc.contributor.author	Guilak, F	en
dc.date.accessioned	2014-03-01T01:30:11Z
dc.date.available	2014-03-01T01:30:11Z
dc.date.issued	2009	en
dc.identifier.issn	00043591	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/19493
dc.subject	Knockout Mice	en
dc.subject.other	collagen type 4	en
dc.subject.other	animal experiment	en
dc.subject.other	animal model	en
dc.subject.other	article	en
dc.subject.other	articular cartilage	en
dc.subject.other	biomechanics	en
dc.subject.other	bone density	en
dc.subject.other	cartilage cell	en
dc.subject.other	joint degeneration	en
dc.subject.other	micropipette	en
dc.subject.other	morphometrics	en
dc.subject.other	mouse	en
dc.subject.other	musculoskeletal system malformation	en
dc.subject.other	nonhuman	en
dc.subject.other	osteoarthritis	en
dc.subject.other	priority journal	en
dc.subject.other	Animals	en
dc.subject.other	Biomechanics	en
dc.subject.other	Bone Density	en
dc.subject.other	Cartilage, Articular	en
dc.subject.other	Collagen Type VI	en
dc.subject.other	Disease Models, Animal	en
dc.subject.other	Disease Progression	en
dc.subject.other	Extracellular Matrix	en
dc.subject.other	Joint Instability	en
dc.subject.other	Mice	en
dc.subject.other	Mice, Knockout	en
dc.subject.other	Osteoarthritis	en
dc.subject.other	Synovial Membrane	en
dc.title	Developmental and osteoarthritic changes in Col6a1-knockout mice: Biomechanics of type VI collagen in the cartilage pericellular matrix	en
heal.type	journalArticle	en
heal.identifier.primary	10.1002/art.24293	en
heal.identifier.secondary	http://dx.doi.org/10.1002/art.24293	en
heal.publicationDate	2009	en
heal.abstract	Objective. Chondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulated by a narrow tissue region termed the ""pericellular matrix"" (PCM), which in normal cartilage is defined by the exclusive presence of type VI collagen. Because the PCM completely surrounds each cell, it has been hypothesized that it serves as a filter or transducer for biochemical and/or biomechanical signals from the cartilage ECM. The present study was undertaken to investigate whether lack of type VI collagen may affect the development and biomechanical function of the PCM and alter the mechanical environment of chondrocytes during joint loading. Methods. Col6a1-/- mice, which lack type VI collagen in their organs, were generated for use in these studies. At ages 1, 3, 6, and 11 months, bone mineral density (BMD) was measured, and osteoarthritic (OA) and developmental changes in the femoral head were evaluated histomorphometrically. Mechanical properties of articular cartilage from the hip joints of 1-monthold Col6a1-/-, Col6a1 +/-, and Col6a1+/+ mice were assessed using an electromechanical test system, and mechanical properties of the PCM were measured using the micropipette aspiration technique. Results. In Col6a1 -/- and Col6a1+/- mice the PCM was structurally intact, but exhibited significantly reduced mechanical properties as compared with wildtype controls. With age, Col6a1-/- mice showed accelerated development of OA joint degeneration, as well as other musculoskeletal abnormalities such as delayed secondary ossification and reduced BMD. Conclusion. These findings suggest that type VI collagen has an important role in regulating the physiology of the synovial joint and provide indirect evidence that alterations in the mechanical environment of chondrocytes, due to either loss of PCM properties or Col6a1-/--derived joint laxity, can lead to progression of OA. © 2009, American College of Rheumatology.	en
heal.journalName	Arthritis and Rheumatism	en
dc.identifier.doi	10.1002/art.24293	en
dc.identifier.volume	60	en
dc.identifier.issue	3	en
dc.identifier.spage	771	en
dc.identifier.epage	779	en