COMP Acts as a Catalyst in Collagen Fibrillogenesis

Abstract

We have previously reported that COMP (cartilage oligomeric matrix protein) is prominent in cartilage but is also present in tendon and binds to collagens I and II with high affinity. Here we show that COMP influences the fibril formation of these collagens. Fibril formation in the presence of pentameric COMP was much faster, and the amount of collagen in fibrillar form was markedly increased. Monomeric COMP, lacking the N-terminal coiled-coil linker domain, decelerated fibrillogenesis. The data show that stimulation of collagen fibrillogenesis depends on the pentameric nature of COMP and not only on collagen binding. COMP interacts primarily with free collagen I and II molecules, bringing several molecules to close proximity, apparently promoting further assembly. These assemblies further join in discrete steps to a narrow distribution of completed fibril diameters of 149 ؎ 16 nm with a banding pattern of 67 nm. COMP is not found associated with the mature fibril and dissociates from the collagen molecules or their early assemblies. However, a few COMP molecules are found bound to more loosely associated molecules at the tip/end of the growing fibril. Thus, COMP appears to catalyze the fibril formation by promoting early association of collagen molecules leading to increased rate of fibrillogenesis and more distinct organization of the fibrils.

Abnormal bone quality in cartilage oligomeric matrix protein and matrilin 3 double‐deficient mice caused by increased tissue inhibitor of metalloproteinases 3 deposition and delayed aggrecan degradation

“…Even though the total amount of type II collagen seemed to be unchanged, the findings of both the antibody staining and the extractability experiments were markedly changed in the absence of COMP and matrilin 3. We speculate that the fibril structure is altered, since both COMP and matrilin 3 bind to collagens and are known to influence fibrillogenesis and collagen volume density, respectively (4,6,9,10,12). Moreover, consistent with the histologic findings, the physical bone parameters obtained from the peripheral QCT measurements showed alterations in the metaphysis, with an elevation of trabecular bone mineral content and density (Table 1).…”

“…COMP and matrilin 3 are two extracellular matrix adaptor proteins with a similar ligand repertoire (7,(9)(10)(11)(12)(13)(14). Mutations in either COMP or matrilin 3 are associated with human diseases that affect skeletal development (15)(16)(17), but development proceeds normally in both COMP and matrilin 3 single-deficient mice, without any pronounced skeletal abnormalities (18,19).…”

“…COMP binds in a zinc-dependent manner to triple-helical types I and II collagen and facilitates their fibrillogenesis. After the collagen fibrils have formed, COMP dissociates from the mature fibril (9,10). It also interacts with a number of other extracellular matrix proteins, including matrilins (3), type IX collagen (11)(12)(13), and aggrecan (14).…”

“…COMP and matrilin 3 not only bind to each other, but they also interact with a similar repertoire of extracellular matrix components, such as types II and IX collagen (9)(10)(11)(12)(13). Given the similar adaptor function, it is possible that they can functionally compensate for each other.…”

When is a thrombogenic matrix not thrombogenic?

“…Classification of both continues to evolve. 4,5 Originally described as "senile EBV-associated lymphoproliferative disorder," renamed "EBV-positive DLBCL of the elderly" for inclusion as a provisional entity in the 2008 World Health Organization classification, 6 the suggested terminology has been revised to acknowledge the occurrence in younger patients. 7 "Of the elderly" has been replaced by "not otherwise specified" (EBV 1 DLBCL, NOS).…”