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Altered endochondral bone development in matrix metalloproteinase 13-deficient mice
The hypothesis that proper ECM remodeling is the dominant rate-limiting process for programmed cell death, angiogenesis and osteoblast recruitment during normal skeletal morphogenesis is supported.
ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro
The data suggest that ADAMts5 may be a suitable target for the development of new drugs designed to inhibit cartilage destruction in arthritis, although further work will be required to determine whether ADAMTS5 is also the major aggrecanase in human arthritis.
Proteoglycans: many forms and many functions
The control of glycosaminoglycan structure is not well understood, but it does appear to be used to change the properties of proteoglycans to suit different biological needs.
Degradation of cartilage aggrecan by collagenase‐3 (MMP‐13)
Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development.
OBJECTIVE To investigate the role of matrix metalloproteinase 13 (MMP-13; collagenase 3) in osteoarthritis (OA). METHODS OA was surgically induced in the knees of MMP-13-knockout mice and wild-type…
The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B.
Hyaluronan synthesis and degradation in cartilage and bone
- E. Bastow, S. Byers, S. Golub, C. Clarkin, A. Pitsillides, A. Fosang
- Biology, EngineeringCellular and Molecular Life Sciences
- 1 February 2008
The role and regulation of HA synthesis and degradation in cartilage, bone and skeletal development is discussed and the functions of HA depend on its intrinsic properties, which in turn rely on the degree of polymerisation by HA synthases, depolymerisation by hyaluronidases, and interactions with HA-binding proteins.
Proteoglycan degradation by the ADAMTS family of proteinases.
Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair.
- C. Little, Clare T. Meeker, A. Fosang
- Biology, MedicineThe Journal of clinical investigation
- 1 June 2007
Blocking cleavage in the IGD not only diminished aggrecan loss and cartilage erosion in surgically induced osteoarthritis and a model of inflammatory arthritis, but appeared to stimulate cartilage repair following acute inflammation.
Monoclonal antibodies that specifically recognize neoepitope sequences generated by 'aggrecanase' and matrix metalloproteinase cleavage of aggrecan: application to catabolism in situ and in vitro.
- C. Hughes, B. Caterson, A. Fosang, P. Roughley, J. Mort
- BiologyThe Biochemical journal
- 1 February 1995
Results demonstrate that 'aggrecanase' activity is not a constitutive event in all cartilage culture systems and suggest that proteolytic agents other than 'aggREcanase" are involved in aggrecan catabolism in normal turnover compared with pathological conditions.