Effect of N-acetylglucosamine on osteoblastic activity and expression of bone morphogenetic protein in fracture healing

Yiqun CUI; Ruowu SHEN

ABSTRACT

BACKGROUND:

Chitin and its derivatives possess many biological activities such as immune modulation and promoting wound healing and hemostasis. As one of the derivatives of chitin, the effect of N-acetylglu cosamine on fracture healing has not yet been acknowledged.

OBJECTIVE:

To observe the changes in osteoblastic activity and the expression of bone morphogenetic protein (BMP) in response to the intervention with N-acetylglucosamine during the fracture healing.

DESIGN:

A randomized controlled experiment

SETTING:

Department of Anatomy, Medical College of Qingdao University.MATERIALS This experiment was carried out in the Laboratory of Neuroanatomy, Medical Colloge of Qingdao University from March to August 2002. Seventy healthy New Zealand rabbits were randomized into four groups, namely saline group (n=23), Jiegupian group (n=23) and N-acetyl glucosamine group (n=24).

METHODS:

The rabbits were subjected to operations to induce 3-mm bone defect in the middle segment of the right radius with subsequent treatments with saline (1.00 mL/kg), Jiegupian (1.00 mL/kg) and N-acetyl glucosamine (0.28 g/kg) via intragastric administration on a daily basis till the time of tissue sampling at postoperative days 9, 17, 30 and 42, respectively. X-ray examination and HE staining were performed to observe the healing process, and the expression of BMP was assessed immunohistochemically.MAIN OUTCOME

MEASURES:

① General condition of the rabbits after operation; ② Fracture healing process revealed by X-ray at the specified time points; ③ Expression of BMP between the fracture ends at each time point; ④ Results of histological observation.

RESULTS:

According to intent-to-treat analysis, 70 rabbits entered the data analysis. X-ray revealed better fracture healing in N-acetylglucosamine group than in the ither two groups at postoperative days 9, 17, 30 and 42(P ＜ 0.05). Compared with saline group, the expression of BMP protein in Jiegupian group and N-acetylglucosamine group was increasing at postoperative 9 and 17 days, particularly in the latter group (P ＜ 0.05), but decreased at postoperative 30 and 42 days. Histologically, the gap between the fracture ends reduced in N-acetylglucosamine group at postoperative 9 days with the appearance of ()bmogenous bone trabecula an orderly arrangement of osteoblasts; in saline group, the gap was greater and contained less or even no bone trabecula, with much less, if any, osteoblasts.On postoperative day 30, the bone defect were completely filled by bone trabecula in N-acetylglucosamine group, with the bone trabecula almost communicating with the bone marrow cavity, and the osteoblasts surrounding the bone trabecula were arranged orderly with osteoclasts seldom observed; in saline group, the defect was substituted mostly by bone trabecula with breaches, and the chondrocytes could be observed scarcely. On postoperative day 42, the bone plate woven bone formed primarily at the fracture ends in N-acetylglucosamine group, with completely communicating marrow cavity and numerous active osteoclasts, and osseous lacuna can be observed; in saline group, the defect was filled with bone trabecula but clear fusion lines were not seen, and communication of the bone marrow cavity was nearly achieved with orderly arranged osteoblasts and presence of the osteoclasts.

CONCLUSION:

N-acetylglucosamine can accelerate fracture healing possibly by promoting the osteoblastic activity and increase the expression of BMP during the early period of fracture healing.