Expression of hypoxia-induced semaphorin 7A correlates with the severity of inflammation and osteoclastogenesis in experimentally induced periapical lesions.
OBJECTIVE
While hypoxia and inflammation are intimately linked, the effects of inflammatory hypoxia on the pathogenesis of periapical lesions remain largely unknown. The aim of this study was to examine hypoxia during the progression of experimentally induced rat periapical lesions, and to derive correlations between hypoxia-induced Semaphorin 7A (Sema7a) expression, severity of inflammation, and osteoclastogenesis in the lesions.


METHODS
Periapical lesions were developed after mandibular first molar pulp exposure in forty Sprague-Dawley rats. The animals were randomly divided into four groups and sacrificed at 0, 7, 14, and 28days after pulpal exposure. The bilateral mandibles containing the first molar were obtained and routinely prepared for histological, immunohistochemical, enzyme histochemical analyses and quantitative polymerase chain reaction detecting Sema7a mRNA expression. Data were analysed by one-way analysis of variance and the Pearson's correlation and linear tendency test.


RESULTS
Periapical tissues become hypoxic during the development of experimentally induced periapical lesions, with steadily increasing numbers of HIF-1α-positive cells that positively correlate with the expression of Sema7a mRNA in the lesions. Furthermore, significant positive correlates were derived for the expression of Sema7a and the degree of inflammatory infiltration and osteoclast number, respectively.


CONCLUSIONS
Hypoxia-induced Sema7a participates in the pathogenesis of periapical lesions, providing a novel therapeutic target for the treatment of this inflammatory disease in the future.
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China.
Miao
M
He
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, 430079, China. Electronic address: bianzhuan@whu.edu.cn.
Zhuan
Z
Bian
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D003786:Dental Pulp Cavity / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000150:complications*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D008334:Mandible; D008963:Molar / Q000293:injuries; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D010483:Periapical Diseases / Q000150:complications* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010486:Periapical Tissue / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D039961:Semaphorins / Q000378:metabolism*
D015703:Antigens, CD; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C558466:Sema7a protein, rat; D039961:Semaphorins
HIF-1α; Hypoxic inflammation; Inflammatory infiltration; Osteoclastogenesis; Periapical lesions; Semaphorin 7A