Bone Research Unit, Medical Research Council/University of the Witwatersrand, Johannesburg, South Africa.
Cell Prolif. 2010 Jun;43(3):207-18. doi: 10.1111/j.1365-2184.2010.00675.x.
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.
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.
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.
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.
使用 4 只成年非人类灵长类动物（熊猴）研究重组人转化生长因子-β2（hTGF-β2）与肌肉来源的干细胞共同诱导骨形成的情况。
将 hTGF-β2 植入到腹直肌中，同时将来自腹直肌或颞肌的横纹肌碎块加入到颅骨缺损处。通过 Northern 印迹分析检测生成标本中的成骨标记物，包括骨形成蛋白-1、骨形态发生蛋白-3 和 IV 型胶原的 mRNA 表达。
将 5μg 和 25μg hTGF-β2 与 100mg 不可溶性胶原骨基质共同植入到异位的肌内，在 30 天可产生大的皮质化矿化骨节，在 90 天出现重塑和造血骨髓诱导。将横纹肌碎块加入到颅骨植入物中可在 90 天内显著增强骨形成的诱导。
与啮齿动物和兔形目动物相比，在熊猴中，hTGF-β2 在植入到腹直肌后的 30 天内可诱导产生大的皮质化和血管化的骨节。这种横纹肌含有反应性干细胞，可增强 hTGF-β2 的骨诱导级联反应。hTGF-β2 在非人类灵长类动物熊猴中诱导骨形成的原因可能是 hTGF-β2 异位植入后表达了骨形态发生蛋白；需要重新评估哺乳动物 TGF-β 蛋白在熊猴中引发的骨诱导级联反应，以用于临床背景下诱导骨形成的新型分子治疗。
