Expression of Bone Morphogenetic Proteins during Mandibular Distraction Osteogenesis

Abstract

Distraction osteogenesis is a form of in vivo tissue engineering in which the gradual separation of cut bone edges results in the generation of new bone. In this study, the temporal and spatial expression of bone morphogenetic proteins (BMPs) 2, 4, and 7 was examined in a rabbit model of mandibular distraction osteogenesis. Fourteen skeletally mature male rabbits were studied. After osteotomy, a distractor was applied to one side of the mandible. After 1 week of latency, distraction was initiated at 0.25 mm every 12 hours for 3 weeks (distraction period), followed by a 3-week consolidation period. Two animals were killed each week after surgery. The generate bone was analyzed for the expression of BMP-2, -4, and -7 by using standard bone histological and immunohistochemical techniques. BMP-2 and -4 were highly expressed in osteoblastic cells during the distraction period and in chondrocytes during the consolidation period. BMP-7 demonstrated relatively minor expression in osteoblastic cells during the distraction period. All BMPs were strongly expressed in vascularized connective tissue during the distraction period. These data indicate that BMPs participate in the translation of mechanical stimuli into a biological response during mandibular distraction osteogenesis.

Stress fracture healing: Fatigue loading of the rat ulna induces upregulation in expression of osteogenic and angiogenic genes that mimic the intramembranous portion of fracture repair

“…Pre-myogenic cells are capable of differentiating into chondrogenic or osteogenic cells when exposed to BMPs [7], and signaling of BMP2 initiating from the vasculature may attract circulating cells of osteoblastic lineage [46]. During distraction osteogenesis, the spatial patterns of VEGF and BMP2 expression are tightly linked [12], and there is a temporal correspondence between BMP2 expression and the amount of vascularized connective tissue in the distraction gap during the first two weeks of distraction [47]. Moreover, inhibition of angiogenesis during distraction osteogenesis [11] and fracture repair [23] prevents bone formation and leads to fibrous non-union.…”

BMP-9 expression in human traumatic heterotopic ossification: a case report

“…Immunohistochemical staining of cellular and extracellular proteins has been used in mandibular [20], long bone distraction osteogenesis [21-24], and bone healing [13-15] studies. We employed this technique to semi-quantitatively evaluate our results based on the percentage of positively stained cells using the following grading scheme: +, 25% of the cells stained positively for the protein of interest; ++, 25 to 50% of the cells stained positively; +++, 50 to 75% of the cells stained positively; ++++, more than 75% of the cells stained positively; -, no cells stained positively.…”

The Molecular and Cellular Events That Take Place during Craniofacial Distraction Osteogenesis

“…18,50 It has been reported that BMP-7 plays a role similar to that of BMP-2 and BMP-4 in distraction osteogenesis 48 ; however, most experiments have detected only weak levels or no expression of BMP-7 during distraction osteogenesis. 19,49,51 …”