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- Soluble, insoluble and geometric signals sculpt the architecture of mineralized tissues

Invited Review

Soluble, insoluble and geometric signals sculpt the architecture of mineralized tissues

U. Ripamonti *

 Bone Research Unit, Medical Research Council, University of the Witwatersrand, Johannesburg, South Africa

* Correspondence to: Professor Ugo RIPAMONTI Bone Research Unit, MRC/University of the Witwatersrand, Johannesburg, 7 York Road, 2193 Parktown, South Africa. Tel./Fax: + 12 11 717 2300 E-mail: [email protected]

Bone morphogenetic and osteogenic proteins (BMPs/OPs), members of the transforming growth factor-β (TGF-β) superfamily, are soluble mediators of tissue morphogenesis and induce de novo endochondral bone formation in heterotopic extraskeletal sites as a recapitulation of embryonic development. In the primate Papio ursinus, the induction of bone formation has been extended to the TGF-β isoforms per se. In the primate and in the primate only, the TGF-β isoforms are initiators of endochondral bone formation by induction and act in a species-, site- and tissue-specific mode with robust endochondral bone induction in heterotopic sites but with limited new bone formation in orthotopic bone defects. The limited inductive capacity orthotopically of TGF-β isoforms is associated with expression of the inhibitory Smads, Smad6 and Smad7. In primates, bone formation can also be induced using biomimetic crystalline hydroxyapatite matrices with a specific surface geometry and without the exogenous application of osteogenic proteins of the TGF-β superfamily, even when the biomimetic matrices are implanted heterotopically in the rectus abdominis muscle. The sequence of events that directs new bone formation upon the implantation of highly crystalline biomimetic matrices initiates with vascular invasion, mesenchymal cell migration, attachment and differentiation of osteoblast-like cells attached to the substratum, expression and synthesis of osteogenic proteins of the TGF-β superfamily resulting in the induction of bone as a secondary response. The above findings in the primate indicate enormous potential for the bioengineering industry. Of particular interest is that biomimetic matrices with intrinsic osteoinductivity would be an affordable option in the local context.

Keywords: bone induction • primates • TGF-β • BMPs/OPs • hydroxyapatite biomimetic matrices • geometry • bioengineering

J. Cell. Mol. Med. Vol 8, No 2, 2004 pp. 169-180  



The initiation of bone formation during embryonic development and postnatal osteogenesis involves a complex cascade of molecular and morphogenetic processes that ultimately lead to the architectural sculpture of precisely organized multicellular structures. These include mineralized bone composed of osteoid which is the novel bone matrix as yet to be mineralized, and cellular elements including osteoblasts or bone forming cells, osteoclasts or remodelling and resorbing cells, and osteocytes, living bone cells within newly formed mineralized bone matrix [1]. Elucidating the nature and interaction of the signalling molecules that direct the generation of tissue-specific patterns during the initiation of bone formation is a major challenge of contemporary molecular, cellular, developmental and tissue engineering biology [2].

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