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BMP4 and Noggin improve bone regeneration

By Anne John Michael

Tissue engineering and regenerative medicine have been used to promote bone healing and improve bone regeneration (Peng & Huard 2004). Most current therapies do not emphasize the importance of imitating the natural healing process that occurs after a fracture. In a natural healing process, expression of growth factors is followed by expression of their specific antagonists (Yoshimura et al 2001). Simultaneous expression of BMP4 and its specific antagonist, Noggin can improve bone regeneration that closely resembles the original tissue that develops during fracture healing. It also exhibits a better control over its effects to prevent undesired bone regeneration and bone overgrowth.

Noggin is delivered by constitute expression and BMP4 is dispended through induced expression. A recent study found that when Noggin is expressed together with BMP4, there is a closer resemblance for the regenerated bone to the original bone than the regeneration process to occur in the absence of Noggin (Peng et al 2005). This is because BMP4 encourages bone regeneration and the muscle-derived stem cells (MDSCs) will continue expressing BMP4 if Noggin is not present and this ultimately leads to bone overgrowth. Noggin not only suppresses the expression of BMP4 but also modulates the activity of BMP4 in the system. Besides the interaction between BMP4 and Noggin, other growth factors produced by the bone regeneration site also plays an important role in a more regulated growth in the injured site.

Peng and his collegues demonstrated their results using skull defects as an example of bone fracture. The dura mater is the connective tissue that lies beneath the skull bone and is important for in inducing osteogenesis (Yu et al 1997). The basic fibroblasts growth factor (bFGF) in the dura mater might increase the osteogenic effects of BMPs by promoting differentiation of osteoblasts (Lee et al 2000). The researchers also found that bone regeneration was rampant in the area near the dura mater primarily because of its high concentrations of growth factors. Areas further away from the dura mater has lesser concentrations of growth factors (Peng et al 2005). Therefore this assures that only the areas with sufficient amount of growth factors will experience bone formation. This particular study is a pioneer effort in ensuring that the bone regrowth almost resembles the processes occurring during fracture healing, with more specific and better regulation.

The findings can also be applied for other tissue engineering and gene therapy to improve the smooth running of these techniques.


Peng H. & Huard J. 2004. Muscle-derived stem cells for musculoskeletal tissue regeneration and repair. Transplant. Immunol.;12: 311 – 319.
Yoshimura Y., et al. 2001. Colocalization of noggin and bone morphogenetic protein-4 during fracture healing. J. Bone Miner. Res.;16: 876 – 884.

Peng H, Usas A, Hannallah D, Olshanski A, Cooper GM & Huard J. 2005. Noggin improves bone healing elicited by muscle stem cells expressing inducible BMP4. Molecular Therapy; 12(2): 239-246

Yu JC., et al. 1997. Regional differences of dura osteoinduction: squamous dura induces osteogenesis, sutural dura induces chondrogenesis and osteogenesis. Plast. Reconstr. Surg.;100: 23 – 31.

Lee JY., et al. 2000. Clonal isolation of muscle-derived cells capable of enhancing
muscle regeneration and bone healing. J. Cell Biol.;150: 1085 – 1100.

Source: Medical Engineering, 02/12/2005

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