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-month-old 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 wild-type 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.
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-month-old 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 wild-type 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.
Authors: A V Ljubimov; R E Burgeson; R J Butkowski; J R Couchman; R R Wu; Y Ninomiya; Y Sado; E Maguen; A B Nesburn; M C Kenney Journal: Invest Ophthalmol Vis Sci Date: 1996-05 Impact factor: 4.799
Authors: Eric J Vanderploeg; Christopher G Wilson; Stacy M Imler; Carrie Hang-Yin Ling; Marc E Levenston Journal: J Anat Date: 2012-06-18 Impact factor: 2.610
Authors: Biao Han; Hadi T Nia; Chao Wang; Prashant Chandrasekaran; Qing Li; Daphney R Chery; Hao Li; Alan J Grodzinsky; Lin Han Journal: ACS Biomater Sci Eng Date: 2017-07-11
Authors: Biao Han; Qing Li; Chao Wang; Pavan Patel; Sheila M Adams; Basak Doyran; Hadi T Nia; Ramin Oftadeh; Siyuan Zhou; Christopher Y Li; X Sherry Liu; X Lucas Lu; Motomi Enomoto-Iwamoto; Ling Qin; Robert L Mauck; Renato V Iozzo; David E Birk; Lin Han Journal: ACS Nano Date: 2019-10-01 Impact factor: 15.881
Authors: B Doyran; W Tong; Q Li; H Jia; X Zhang; C Chen; M Enomoto-Iwamoto; X L Lu; L Qin; L Han Journal: Osteoarthritis Cartilage Date: 2016-08-25 Impact factor: 6.576