Matrix vesicles are carriers of bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and noncollagenous matrix proteins

Abstract

Matrix vesicles (MVs) are well positioned in the growth plate to serve as a carrier of morphogenetic information to nearby chondrocytes and osteoblasts. Bone morphogenetic proteins (BMPs) carried in MVs could promote differentiation of these skeletal cells. Vascular endothelial growth factor (VEGF) in MVs could stimulate angiogenesis. Therefore, a study was undertaken to confirm the presence of bone morphogenetic protein (BMP)-1 through-7, VEGF, and the noncollagenous matrix proteins, bone sialoprotein (BSP), osteopontin (OPN), osteocalcin (OC), and osteonectin (ON) in isolated rat growth plate MVs. MVs were isolated from collagenase-digested rachitic rat tibial and femoral growth plates. The presence of BMP-1 through BMP-7, VEGF, BSP, ON, OPN, and OC was evaluated by Western blot, plus ELISA analyses for BMP-2 and-4 content. The alkaline phosphatase-raising ability of MV extracts on cultured rat growth plate chondrocytes was measured as a reflection of MV ability to promote chondroosseous differentiation. BMP-1 through-7, VEGF, BSP, ON, OPN, and OC were all detected by Western blot analyses. Chondrocytes treated with MV extracts showed a two-to threefold increase in alkaline phosphatase activity over control, indicating increased differentiation. Significant amounts of BMP-2 and BMP-4 were detected in MVs by ELISA. Combined, these data suggest that MVs could play an important morphogenetic role in growth plate and endochondral bone formation.

The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling

“…This certainly seems convincing as numerous studies have documented BSP, which is localised to MVs, to be involved in the initial formation of HA (Harris et al 2000, Fisher et al 2001, Tye et al 2003, Wang et al 2006, Nahar et al 2008. Indeed, the Bsp null mouse displays shorter, hypomineralised bones with associated higher trabecular bone mass with low bone turnover (Malaval et al 2008).…”

Roles of High Mobility Group Box 1 in Cardiovascular Calcification

“…First, in matrix vesicles, influx of calcium and phosphate via annexins and sodium-dependent inorganic phosphate transporters, respectively, leads to initial mineral accumulation in the form of hydroxyapatite crystals near the membrane. Second, mineral propagation in the ECM occurs, whereby hydroxyapatite crystals grow within the vesicles until the membrane ruptures; once exposed to the ECM, the crystals act as loci or templates for the formation of new crystals via homologous nucleation [85-88]. Alexander et al observed that matrix vesicles released by VSMCs are also exosomal-like vesicles and that increased exosome release promotes cardiovascular calcification in response to environmental calcium stress [89].…”

“…Emerging evidence suggests that calcification may be initiated by the release of calcifying extracellular vesicles from cells residing in the calcification niche [80]. Matrix vesicles were initially found to be secreted from hypertrophic chondrocytes and osteoblasts during osteogenesis [85], initiating mineralization in two phases. First, in matrix vesicles, influx of calcium and phosphate via annexins and sodium-dependent inorganic phosphate transporters, respectively, leads to initial mineral accumulation in the form of hydroxyapatite crystals near the membrane.…”

RALA complexed α-TCP nanoparticle delivery to mesenchymal stem cells induces bone formation in tissue engineered constructs in vitro and in vivo

“…The unique organization of mineralized collagen matrix provides structural integrity and mechanical strength to bone. The role of CaP-containing vesicles in the matrix mineralization has been previously established 28,[32][33][34]70 . This suggested that the release of Ca 2+ and PO For example, it might enable shortening of the in vitro priming time necessary to engineer hypertrophic cartilage templates suitable for bone regeneration.…”