Induction of bone formation by transforming growth factor-beta2 in the non-human primate Papio ursinus and its modulation by skeletal muscle responding stem cells.
OBJECTIVE
Four adult non-human primates Papio ursinus were used to study induction of bone formation by recombinant human transforming growth factor-beta(2) (hTGF-beta(2)) together with muscle-derived stem cells.


METHODS
The hTGF-beta(2) was implanted in rectus abdominis muscles and in calvarial defects with and without addition of morcellized fragments of striated muscle, harvested from the rectus abdominis or temporalis muscles. Expression of osteogenic markers including osteogenic protein-1, bone morphogenetic protein-3 and type IV collagen mRNAs from generated specimens was examined by Northern blot analysis.


RESULTS
Heterotopic intramuscular implantation of 5 and 25 microg hTGF-beta(2) combined with 100 mg of insoluble collagenous bone matrix yielded large corticalized mineralized ossicles by day 30 with remodelling and induction of haematopoietic marrow by day 90. Addition of morcellized rectus abdominis muscle to calvarial implants enhanced induction of bone formation significantly by day 90.


CONCLUSIONS
In Papio ursinus, in marked contrast to rodents and lagomorphs, hTGF-beta(2) induced large corticalized and vascularized ossicles by day 30 after implantation into the rectus abdominis muscle. This striated muscle contains responding stem cells that enhance the bone induction cascade of hTGF-beta(2). Induction of bone formation by hTGF-beta(2) in the non-human primate Papio ursinus may occur as a result of expression of bone morphogenetic proteins on heterotopic implantation of hTGF-beta(2); the bone induction cascade initiated by mammalian TGF-beta proteins in Papio ursinus needs to be re-evaluated for novel molecular therapeutics for induction of bone formation in clinical contexts.
Ripamonti
U
U
Bone Research Unit, Medical Research Council/University of the Witwatersrand, Johannesburg, South Africa. ugo.ripamonti@wits.ac.za
Roden
L C
LC
D000818:Animals; D001857:Bone Matrix / Q000737:chemistry / Q000378:metabolism / Q000637:transplantation; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D009999:Ossification, Heterotopic / Q000139:chemically induced / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D048549:Papio ursinus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D017568:Rectus Abdominis / Q000166:cytology / Q000187:drug effects / Q000601:surgery; D015398:Signal Transduction / Q000502:physiology; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000601:surgery; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D016042:Transplantation, Heterotopic / Q000379:methods; D016896:Treatment Outcome
D019485:Bone Morphogenetic Proteins; D011993:Recombinant Fusion Proteins; D053781:Transforming Growth Factor beta2