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Background. To find a better prophylactic regimen, the pathogenesis of acquired heterotopic ossification (AHO) must be more understood. To date, AHO formation is largely thought to be related to inflammation, which is activated by trauma, resulting in AHO by up-regulation of pro-osteogenic genes. Methods. Brain-traumatic/burn/tenotomy model is firstly used in experiment. At first, 44 rats were randomly divided into two groups: E group and C group. Two rats in every group were euthanized during second, third, fourth, sixth, eighth, tenth weeks for collecting tendon. The remaining rats survived until tenth week for X-Ray radiation examination to confirm the size of AHO.Then, 124 rats were randomly divided into four group: P group, L group, M group, H group. The three rats of every group were euthanized during every week of the first seven weeks for collecting tendon to detect P65 protein. The remaining rats survived until tenth week for X-Ray examination to confirm the size of AHO. Results. The success rate of Brain-traumatic/Burn/Tenotomy model is 100%. Difference of P65 expression in E group and in C group are statistically significant,and that in E group is higher.Pharmacologic inhibition of Nf-ҝb signaling pathway limits AHO formation, and that The bone formation content of M group is decreased. Conclusion. Brain-traumatic/Burn/Tenotomy model is highly reliable.Results indicate that the Nf-ҝb /p65 signaling response occurs in the forming process of AHO. PDTC limits formation of AHO. The most effective concentration is 6mg/ml for local injection.

We investigated the role of fetuin A during heterotopic ossification (HO) in rats following Achilles tenotomy. We performed a right midpoint Achilles tenotomy on 24 rats. At 5 and 10 h after surgery, we investigated the formation of ectopic bone using X-ray and histological examination. We evaluated the mRNA level of fetuin A using real-time PCR. Presence of fetuin A in the Achilles tendon was assessed by immunohistochemical staining. We also measured the serum concentration of fetuin A using enzyme linked immunosorbent assay (ELISA). The expression of fetuin A was significantly decreased in both the liver and Achilles tendon during HO. ELISA showed a small amount of fetuin A in blood throughout the development of HO. Immunohistochemical staining showed that fetuin A was abundant in the ectopic bone. Fetuin A appears to be involved in the formation of ectopic bone induced by Achilles tenotomy, and a deficiency of fetuin A plays a role in the development of HO.

To explore the value of matrix metalloproteinase 9 (MMP-9) in predicting the occurrence of heterotopic ossification by observing the expression of MMP-9 in heterotopic ossification of the early trauma rat model.A total of 132 male Sprague Dawley rats, aged 4-5 weeks, weighing (135.0 ± 6.5) g, were randomly divided into experimental group and control group (n = 66). In experimental group, the Achilles tendon was cut off and clamped to prepare heterotopic ossification model; in control group, only Achilles tendon was exposed by making a incision. The general condition of the rats was observed after operation; at 2, 3, 4, 5, 6, 7, and 8 days after operation, the Achilles tendon tissue was harvested for gross observation, histological observation, and immunohistochemical staining observation; the serum and Achilles tendon tissue were harvested to detect the expressions of MMP-9 protein and mRNA by ELISA and RT-PCR. The X-ray films at 5 and 10 weeks and histological examination at 10 weeks after operation were used to observe heterotopic ossification.All rats survived to the end of the experiment. The Achilles tendon had no significant change in control group at each time point, showing normal tendon structure. In experimental group, the hardness of Achilles tendon tissue gradually increased with the time; there were a large number of irregular connective tissue and cartilage cells; and immunohistochemical staining for MMP-9 was positive results. The MMP-9 protein and mRNA expression levels of experimental group were significantly higher than those of the control group at each time point (P0.05). MMP-9 protein and mRNA expression levels of experimental group showed an increasing tendency (P0.05). According to the results of X-ray films and histological observation, heterotopic ossification occurred at 10 weeks after operation in experimental group, but no heterotopic ossification was observed in control group.In early heterotopic ossification of rat Achilles tendon, the expression of MMP-9 increases significantly, indicating that it has reference significance in predicting heterotopic ossification.

To compare the efficacy of selective cyclooxygenase 2 (COX2) inhibitor and non-selective COX2 inhibitor drugs in prevention of heterotopic ossification in rats model so as to provide reference for clinical drugs selection of heterotopic ossification prevention.Fifty male Sprague Dawley rats, 6 to 8 weeks old, weight (190.0 +/- 8.5) g, were selected; the right Achilles tendon was cut off to induce ectopic bone formation. The rats were randomly divided into 5 groups (n = 10): on the 1st day after modeling, celecoxib was given in groups A [2 mg/(kg x d)] and B [10 mg/(kg x d)], indomethacin in groups C [(2 mg/(kg x d) and D [10 mg/(kg x d)], and 2 mL of saline in group E for 10 weeks. The general condition of rats was observed after operation. At 5 and 10 weeks after operation, X-ray films of the right lower limb were taken to observe new bone formation. At 10 weeks after operation, the right Achilles tendon tissue was harvested for histological observation. Based on X-ray and histological results, heterotopic ossification was assessed. Immunohistochemical staining was used to evaluate COX2 and bone morphogenetic protein 2 (BMP-2) expression levels in local Achilles tendon.During the experiment, 5 rats died (2 in group B, 1 in group C, and 2 in group D), the other rats survived to the end of the experiment. General observation of Achilles tendon tissue showed that the tendon tissue volume of group B was the smallest, with soft texture and no cartilage-like tissue; the tendon tissue volume of group E was the biggest, with hard texture and cartilage-like tissue. The incidence of heterotopic ossification was 80.0% (8/10), 25.0% (2/8), 88.9% (8/9), 50.0% (4/8), and 100% (10/10) in groups A-E respectively at 10 weeks after operation; significant differences were found between groups B, D and group E (P = 0.002, P = 0.023) and between groups B and C (P = 0.015), but no significant difference was found among the other groups (P0.05). COX2 expression level in groups B and D was significantly lower than that in group E (P0.05 ), but no significant difference was found among the other groups (P0.05); BMP-2 expression level in group B was significantly lower than that in groups A, C, and E (P0.05), but no significant difference was found among the other groups (P0.05).Celecoxib at a dose of 10 mg/(kg x d) can effectively reduce the incidence of heterotopic ossification in rats.