집토끼 하악골에서 신연 골형성술시 BMP-2,-4의 발현 = EXPRESSION OF BMP-2, -4 DURING DISTRACTION OSTEOGENESIS IN THE RABBIT MANDIBLE

다국어 초록 (Multilingual Abstract)

Distraction osteogenesis(DO) is defined as a gradual mechanical process of mechanical stretching two vascularized bone surface apart with a critical rate and rhythm such that new bone forms within the expanding gap, reliably bridges the gap, and ultimately remodels to normal structure. DO has become a mainstay in bone tissue engineering and has significantly improved our armamentarium for reconstructive craniomaxillofacial procedures.
But the molecular and biological mechanisms that regulate the formation of new bone during distraction osteogenesis are not completely understood.
BMPs are potent osteoinductive agents.
Our hypothesis was that BMPs, especially BMP-2 and BMP-4, might play an importent role in the signaling pathways that link the mechanical forces created by distraction to biological responses and in promting new bone formation. Using a rabbit’s mandible, we investigated the expression of BMP-2, -4 at different time points during distraction osteogenesis.
The purpose of this study is to research the pattern of expression of BMP-2, -4 in new bone formation during distraction osteogenesis of the rabbit mandible. The experimental group was applied gradual distraction (0.7mm a day by twice a day, 4.9mm in total, for 7 days) and the control group was carried out osteotomy alone. They were examined clinically, histologically, and by RT-PCR analysis.
On 3 days after osteotomy, the high level of expression of BMP-2, -4 was detected. But, the expression of BMP-4 was decreased during latency period. As distraction was started, its expression was increased and maintained till postoperative 28days. In control group, the expression of BMP-4was remarkably decreased till postoperative 14 days. On the other hand, the expression of BMP-2 was no difference between experimental group and control group. The expression of BMP-4 was maintanined at high level during the entire experimental period in both group.
These findings suggested that excellent bone formation during distraction osteogenesis is associated with enhanced expression of BMP-4 genes by mechanical tension stress.

참고문헌 (Reference)

1 "신연골 형성술과 골절 치유에서 제2형 및 제4형 골형성 단백 유전자 mRNA의 시간적,공간적 발현" 33 : 595-603, 1998

2 "신연 골형성술에 있어서의 분자생물학적 최신지견" 28 : 456-463, 2002

3 "The tension-stress effect on the genesis and growth of tissues The influence of the rate and frequency of distraction" clinorthop1989b

4 "The tension-stress effect on the genesis and growth of tissues The influence of stability of fixation and soft-tissue preservation" clinorthop1989a

5 "The molecular biology of distraction osteogenesis" 30 : 1-11, 2002

6 "Temporal and Spatial expression of BMP-2 -4 and -7 during distraction osteogenesis in rabbits" 27 : 453-459, 2000

7 "TGF-beta, BMPs, and their signal transducing mediators, Smads, in rat fracture healing" 60 : 392-397, 2002

8 "Recombinant Human Bone BMP-2 for Maxillary Sinus Grafting 상악동이식술" 정원사 159-170, 1999

9 "Ovariectomy selectively reduces the concentration of TGFb in rat bone:implications for estrogen deficiency-associated bone loss" 89 : 12190-12193, 1992

10 "Osteoinduction Proteins" 25 : 395-402, 1993

11 "Orthopaedic knowledge update" 30-32, 1999

12 "Novel regulators of bone formation:Molecular clones and activities" 242 : 1528-1534, 1988

13 "Mechanical tension-stress induces expression of BMP-2 and BMP-4,but Not BMP-6,BMP-7 and GDF-5 mRNA during distraction osteogenesis" 14 : 1084-1095, 1999

14 "Mechanical induction of osteogenesis the importance of pin rigidity" 396-401,

15 "Immunolocalization and expression of BMP-2 and -4 in fracture healing" 13 : 357-367, 1995

16 "IGF-I,TGF-b and BMP-4 are expressed during distraction osteogenesis of the pig mandible" 31 : 173-178, 2002

17 "Gene expression during autograft lumbar spine fusion and the effect of Bone Morphogenetic Protein 2" 351 : 252-265, 1998

18 "Expression of BMPs during mandibular distraction osteogenesis" 111 : 201-208, 2003

19 "Expression of BMP-4 mRNA during distraction osteogenesis in rabbits" 69 : 42-45, 1998

20 "Effects of TGFb on bone nodule formation and expression of BMP-2 and type 1 collagen mRNA in long-term cultures of fetal rat calvarial osteoblasts" 855-863,

21 "Bone regeneration" 9 : 157-165, 2001

22 "Bone morphogenetic proteins. Principles of Bone Biology" Academic Press Inc. 661-671, 1996

23 "Bone consolidation is enhanced by rhBMP-2 in a rabbit model of distraction osteogenesis" 20 : 779-788, 2002

24 "Bone Formation by autoinduction" 150 : 893-899, 1965