Bone Morphogenetic Protein 9: A Potent Modulator of Cartilage Development In Vitro

Abstract

Few publications describe the activity of bone morphogenetic protein-9 (BMP-9), but the consensus of these largely in vivo studies is that while BMP-9 can induce ectopic bone formation at relatively large concentrations, it is primarily active in non-skeletal locations--including the liver, nervous system and marrow. To study the effects of BMP-9 on chondrogenesis in a well-defined environment, calf articular chondrocytes were seeded onto biodegradable PGA scaffolds. The resulting cell-polymer constructs were cultured in either control medium or medium supplemented with 1, 10, 50 or 100 ng/ml of BMP-9. After 4 weeks of in vitro culture, all concentrations of BMP-9 increased the total mass of the constructs, and the amounts of collagen, glycosaminoglycans (GAG) and cells per construct. On a mass percentage basis, BMP-9 tended to increase GAG, to decrease the relative amount of collagen and had little effect on the relative amount of cells. BMP-9 elicited qualitatively similar responses as BMP-2, -12 and -13. However, in contrast to BMP-12 and -13, BMP-9 (at concentrations > or = 10 ng/ml) induced hypertrophic chondrocyte formation and was the only BMP tested to induce mineralization. Taken together, these data suggest that BMP-9 is a potent modulator of cartilage development in vitro.

Near infrared spectroscopic assessment of developing engineered tissues: correlations with compositional and mechanical properties

“…10, 14–17 The quality of engineered cartilage can be affected by a wide variety of factors such as source of cells and scaffolds characteristics 18 , the effects of which have been explored using biodegradable polymeric scaffolds such as polyglycolic acid (PGA). 19–22 Addition of growth factors has been shown to enhance cartilage regeneration by promoting chondrogenesis, 23–26 increasing chondrogenic differentiation of mesenchymal stem cells, and increasing the expression of cartilage matrix components including type II collagen and aggrecans. 27 Mechanical stimulation via hydrostatic pressure 17 or ultrasound 28–30 has also been shown to augment matrix production from chondrocytes, with these effects having been shown to be further augmented in certain circumstances by the addition of BMP-2 and BMP-4.…”

Nanoparticulate Mineralized Collagen Scaffolds and BMP‐9 Induce a Long‐Term Bone Cartilage Construct in Human Mesenchymal Stem Cells

“…Of note, BMP-9 was uniformly more effective than BMP-2 at inducing expression of cartilage genes at the same dosage. Thus, BMP-9 is potentially both the most osteogenic and the most chondrogenic bone morphogenetic protein in pluripotent cell types [12] . This duality in function may be harnessed in tissue engineering strategies especially in combination tissues such as the osteochondral junction.…”

Protein-based tissue engineering in bone and cartilage repair

“…BMP-2, BMP-12 and BMP-13 all promoted chondrogenic markers in cultures of bovine chondrocytes seeded on scaffolds [53]. Both BMP-2 and BMP-9 have been shown to increase cartilage markers in human mesenchymal stem cells [54,55]. In cultures of human articular chondrocytes, BMP-7 appeared to be superior to IGF-I in stimulating proteoglycan synthesis, although there was an additive effect of supplying both factors [56].…”