Cartilage‐Derived Morphogenetic Proteins and Osteogenic Protein‐1 Differentially Regulate Osteogenesis

  title={Cartilage‐Derived Morphogenetic Proteins and Osteogenic Protein‐1 Differentially Regulate Osteogenesis},
  author={Ludwig Erlacher and John E. McCartney and Ester Piek and Peter ten Dijke and Masaki Yanagishita and Hermann Oppermann and Frank P. Luyten},
  journal={Journal of Bone and Mineral Research},
Cartilage‐derived morphogenetic proteins‐1 and ‐2 (CDMP‐1 and CDMP‐2) are members of the bone morphogenetic protein (BMP) family, which play important roles in embryonic skeletal development. We studied the biological activities of recombinant CDMP‐1 and CDMP‐2 in chondrogenic and osteogenic differentiation and investigated their binding properties to type I and type II serine/threonine kinase receptors. In vivo, CDMP‐1 and CDMP‐2 were capable of inducing dose‐dependently de novo cartilage and… 

Cartilage‐derived morphogenetic proteins enhance the osteogenic protein‐1‐induced osteoblastic cell differentiation of C2C12 cells

Exogenous CDMP‐1, ‐2, and ‐3 synergistically and dose‐dependently enhanced OP‐1 action in stimulating alkaline phosphatase (AP) activity and osteocalcin (OC) mRNA expression and one mechanism of the observed synergy involved enhancement of the induced Smad5 protein expression.

Cartilage‐derived morphogenetic proteins induce osteogenic gene expression in the C2C12 mesenchymal cell line

The three CDMPs appear to be able to stimulate the C2C12 cells to differentiate into the osteoblast pathway and change the expression profile of different members of the BMP family in a similar temporal pattern.

Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells.

The data indicate that CDMP-1,CDMP-2, BMP-6 and OP-1 enhance the osteogenic phenotype in BMSC, with CDMPs being clearly less osteogenic than BMPs.

Osteogenic protein‐1 (OP‐1, BMP‐7) induces osteoblastic cell differentiation of the pluripotent mesenchymal cell line C2C12

The present results indicate that OP‐1 is a potent inducer of C2C12 differentiation into osteoblastic cells.

Effects of cartilage-derived morphogenetic proteins and osteogenic protein-1 on osteochondrogenic differentiation of periosteum-derived cells.

The results indicate that distinct members of the BMP-family increase the mitotic and metabolic activity of periosteum-derived cells and suggests that these growth factors might contribute to the local regulation of bone formation and fracture repair.

Differential effects of osteogenic protein‐1 (BMP‐7) on gene expression of BMP and GDF family members during differentiation of the mouse MC615 chondrocyte cells

The observations suggest that OP‐1 action on cartilage differentiation involves a complex regulation of gene expression of several members of the BMP and the GDF family.

Stimulatory effects of distinct members of the bone morphogenetic protein family on ligament fibroblasts

The preferential expression of cartilage markers in vitro suggests that CDMP-1,CDMP-2, BMP-7, and B MP-6 have the potential to induce differentiation towards a chondrogenic phenotype in ligament fibroblasts.

The role of BMP‐7 in chondrogenic and osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in vitro

BMP‐7 is not a singular lineage determinant, rather it promotes both chondrogenic and osteogenic differentiation of MSCs by co‐ordinating with initial lineage‐specific signals to accelerate cell fate determination.

Differential Temporal Expression of Members of the Transforming Growth Factor β Superfamily During Murine Fracture Healing

  • T. ChoL. GerstenfeldT. Einhorn
  • Biology
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2002
Bone morphogenetic protein 2 (BMP‐2) and growth and differentiation factor 8 (GDF8) showed maximal expression on day 1 after fracture, suggesting their roles as early response genes in the cascade of healing events, and restricted expression of GDF8 to day 1 suggests that it may similarly regulate cell differentiation early in the fracture healing process.

Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis.

CDMPs and OP-1 exert their anabolic effects on both healthy and osteoarthritic chondrocytes indicating no loss in responsiveness to these growth factors in OA.



Recombinant bone morphogenetic protein-4, transforming growth factor-beta 1, and activin A enhance the cartilage phenotype of articular chondrocytes in vitro.

BMP-4 and TGF-beta 1 increased the levels of expression of type II collagen and proteoglycan aggrecan in short-term cultures, while activin A and inhibin A did not affect these parameters significantly when compared to serum-free control cultures.

Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage [published erratum appears in J Cell Biol 1995 Feb;128(4):following 713]

Results indicate that BMP-2 specifically converts the differentiation pathway of C2C12 myoblasts into that of osteoblast lineage cells, but that the conversion is not heritable.

Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.

Results suggest thatALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALk-2 is a type I receptor shared by activin and OP- 1, but not by B MP-4.

Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells.

It is shown that OP-1 acts on early stage mesenchymal progenitor cells (ATDC5, C3H10T1/2) to induce chondroblastic differentiation, while OP- 1 strongly enhances the osteoblastic phenotype of committed osteoblasts (MC3T3-E1), possibly explaining its induction of the endochondral ossification cascade in vivo.

Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs.

The results suggest that the action of GDF5 may be relatively specific for chondrogenesis during the entire process of the endochondral bone formation.

Stimulation of the expression of osteogenic and chondrogenic phenotypes in vitro by osteogenin.

The present experiments demonstrate the significant influence of osteogenin in the stimulation of osteogenic and chondrogenic phenotypes in vitro.

BMP signaling during bone pattern determination in the developing limb.

Although the bone pattern was not disturbed by expressing individual dominant-negative BRK independently, preferential distal and posterior limb truncations resulted from co-expressing the dominant- negative forms of BRK-2 andBRK-3 in the whole limb bud, thus providing evidence that BMPs are essential morphogenetic signals for limb bone patterning.

Cartilage-derived morphogenetic proteins. Key regulators in chondrocyte differentiation?

  • F. Luyten
  • Medicine, Biology
    Acta orthopaedica Scandinavica. Supplementum
  • 1995
Biological regeneration of tissues can be considered a feasible goal in modern medicine largely because of scientific advances in this past decade. These advances clearly demonstrate that the