Recombinant human bone morphogenetic protein induces bone formation.

Abstract

We have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A doseresponse and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 ,ug of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage-and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans.The therapeutic potential for bone formation induced by demineralized bone or its extracts has long been recognized (1-4), but the definition of the factor(s) responsible has remained elusive. We previously described the molecular cloning of the genes for bone morphogenetic protein (BMP) 1, 2A, 2B, and 3, using peptide sequence information from a group of proteins purified from such an extract (5, 6). Each of these proteins was implicated in cartilage and bone formation by preliminary experiments which demonstrated in vivo cartilage induction at 7 days (5) in the rat ectopic bone-formation system (7). We now describe the purification and characterization of recombinant human BMP-2A, produced by a Chinese hamster ovary (CHO) cell line, and its activity in ectopic bone formation. METHODS 2220The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Functional implication of BMP4 expression on angiogenesis in malignant melanoma

“…The first BMPs were purified from bone extract and showed the ability to induce ectopic bone and cartilage formation in vivo (Wozney et al, 1988;Wang et al, 1990). Today, more than 30 members of the BMP superfamily have been identified in various tissues and species, and it is known that they control a broad range of biological activities in many cell types like epithelial, mesenchymal or neuronal cells (Mehler et al, 1997;Turgeman et al, 2001).…”

Effect of systemic calcium deficiency on the expression of transforming growth factor‐β in chick embryonic calvaria

“…In particular, the BMPs (bone morphogenetic proteins) derived from bone matrix, which are members of the TGF-p superfamily, have been shown to be chondro-and osteo-inductive factors in vivo and in vitro (Wang et al, 1990). TGF-P has also been shown to promote cartilage and bone growth when introduced subperiosteally (Noda and Camilliere, 1989;Joyce et al, 1990).…”

Nanogel‐based scaffold delivery of prostaglandin E2 receptor–specific agonist in combination with a low dose of growth factor heals critical‐size bone defects in mice

“…The novel advantages of our system are as follows. First, a simple chemical of EP4A in combination with low-dose BMP-2 (which cannot induce bone repair by itself [2,22]) significantly induced bone formation in critical-size defects. Second, although low-dose BMP-2 (0.5 g) was needed for this system, the dose was reduced by ϳ75% compared to that used in our previous studies (in which at least 2 g of BMP-2 was required) due to the combination with EP4A.…”

“…However, PGE 2 causes severe side effects systemically, and 3 daily injections of PGE 2 for several weeks are required to stimulate bone formation (9). The anabolic action of PGE 2 in target cells is mediated by G protein-coupled receptor subtypes, including EP1, EP2, EP3, and EP4.…”