Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes

Abstract

Objective. To study the effects of recombinant human osteogenic protein-1 (rHuOP-1; bone morphogenetic protein-7) on proteoglycan and collagen synthesis by human articular chondrocytes.Methods. Articular chondrocytes from fetal, adolescent, and adult human donors were cultured in alginate beads for 4 days in a mixture of Ham's F-12, Dulbecco's modified Eagle's medium, 10% fetal bovine serum (FBS), then for an additional 3-10 days in the presence and absence of rHuOP-1, with and without FBS. Chondrocyte synthetic activity was measured as the amount of incorporation of 35S-sulfate into proteoglycans and 3H-proline into hydroxyproline. Sieve chromatography and sodium dodecyl sulfatepolyacrylamide gel electrophoresis were performed to identify specific proteoglycans and collagens.Results. Recombinant human OP-1 markedly stimulated the synthesis of proteoglycans (mostly aggrecan) and collagens (predominantly type 11) by all chonSupported by NIH grants 2-P50-AR-39239 and AG-04736, an arthritis grant from Werk Kalle Albert (Hoechst AG, Germany), a fellowship from the German Academic Exchange Service (DAAD) (Dr. Huch), and a research fellowship from Opfermann AG, Germany (Dr. Flechtenmacher).Johannes Submitted for publication December 14, 1995; accepted in revised form June 10, 1996. drocyte preparations. This did not require the presence of FBS and was associated with continued expression of the chondrocyte phenotype.Conclusion. Recombinant human OP-1 is a more potent stimulator of the synthesis of cartilage-specific molecules by human articular chondrocytes than are other factors tested for comparison, including TGFPl and activin A.Bone morphogenetic proteins (BMPs), also called osteogenic proteins (OPs), were originally isolated from bone and were shown to induce new bone formation in the rat subcutaneous bone induction model (1-4). Several members of this family (BMPs 2-9) have been identified, and their corresponding genes cloned from human complementary DNA libraries (4-9). The amino acid sequences of these proteins show a highly conserved 7-cysteine domain at the C-terminal end, which suggests that they are members of the transfoming growth factor P (TGFP) superfamily, which includes

Differences in matrix accumulation and hypertrophy in superficial and deep zone chondrocytes are controlled by bone morphogenetic protein

“…We and others have reported that exogenous BMPs also increase matrix synthesis by chondrocytes (Flechtenmacher et al, 1996;Hidaka et al, 2003;Hidaka et al, 2001;Huch et al, 1997;Sailor et al, 1996). In the current study, we have identified SZC as the sub-population that is particularly responsive, even to low doses of BMPs.…”

“…In particular, we and others have shown the efficacy of bone morphogenetic protein-7 (BMP7, also known as osteogenic protein-1) in increasing matrix production in chondrocytes (Flechtenmacher et al, 1996;Hidaka et al, 2001;Huch et al, 1997;Masuda et al, 2006;Merrihew et al, 2003). The BMPs are a family of growth factors whose expression is critical for skeletal development, including the formation of the joints Francis-West et al, 1999;Rosen, 2006).…”

Periodic knee injections of BMP‐7 delay cartilage degeneration induced by excessive running in rats

“…The effects of BMP-7 on cartilage can be explained by two different mechanisms: enhance- ment of cartilage matrix synthesis, and inhibition of cartilage degeneration. Several in vitro studies indicated that BMP-7 promoted the production of type II collagen and proteoglycans in chondrocytes derived from normal 8 and osteoarthritic patients. 9 On the other hand, BMP-7 suppressed the IL-1-induced catabolism in explant culture of human articular cartilage 10 and aggrecanase in a rabbit model.…”

Effects of recombinant human osteogenic protein 1 on the production of proteoglycan, prostaglandin E2, and interleukin‐1 receptor antagonist by human articular chondrocytes cultured in the presence of interleukin‐1β

“…A recent report showed that OP-3 is a more potent stimulator of the synthesis of cartilage-specific collagens and proteoglycans by human articular chondrocytes than are factors such as insulin-like growth factor 1 (IGF-l), TGFP1, and activin, since it was the only factor able to stimulate chondrocytes beyond the levels of synthesis obtained in the presence of 10% FBS (2). The other factors demonstrated stimulation beyond control levels only in serumfree medium (2). The results presented here extend that finding by showing that OP-1 is also effective in stimulating "S-proteoglycan synthesis by chondrocytes maintained in the presence of IL-1p at 10 p g h l .…”