title: Hemokinin-1 competitively inhibits substance P-induced stimulation of osteoclast formation and function.
abstract: Hemokinin-1 (HK-1) is a novel member of the tachykinin family that is encoded by preprotachykinin 4 (TAC4) and shares the neurokinin-1 receptor (NK1-R) with substance P (SP). Although HK-1 is thought to be an endogenous peripheral SP-like endocrine or paracrine molecule in locations where SP is not expressed, neither the distribution of HK-1 in the maxillofacial area nor the role HK-1 in bone tissue have been examined. In this study, we investigated the distribution of HK-1 in trigeminal ganglion (TG) and maxillary bone, and assessed the expression of HK-1 during osteoclast differentiation. In vivo, rat molars were loaded for 5 days using the Waldo method. In vitro, rat osteoclast-like cells were induced from bone marrow cells. HK-1 distribution and expression were examined by immunofluorescence staining and reverse transcription polymerase chain reaction (RT-PCR). In vivo, HK-1 was localized in rat TG neurons; however, the number of HK-1-positive neurons was less than that of SP-positive neurons. In the maxillary bone, nerve fibers, blood vessels, and osteocytes were immunopositive for HK-1. Furthermore, HK-1-positive immunoreactivity was found in osteoclasts on the pressure side. In vitro, PCR showed that TAC4 and NK1-R mRNA was expressed in osteoclasts as well as in bone marrow cells. Although SP (10⁻⁷ M) treatment led to an increased number of osteoclasts, HK-1 (10⁻⁷ M) treatment did not. The numbers of biotin-labeled HK-1 peptides bound osteoclasts significantly decreased upon incubation with unlabeled SP and biotin-labeled HK-1 compared with biotin-labeled HK-1 alone. These results suggest that HK-1 may not stimulate the differentiation and function of osteoclasts. SP-stimulated osteoclast formation is competitively regulated by peripheral HK-1 through NK1-Rs.
authors: Division of Orofacial Functions and Orthodontics, Kyushu Dental University, Kitakyushu 803-8580, Japan.
authors: Aya
authors: A
authors: Fukuda
authors: Tetsuya
authors: T
authors: Goto
authors: Kayoko N
authors: KN
authors: Kuroishi
authors: Kaori K
authors: KK
authors: Gunjigake
authors: Shinji
authors: S
authors: Kataoka
authors: Shigeru
authors: S
authors: Kobayashi
authors: Kazunori
authors: K
authors: Yamaguchi
mesh_terms: D000818:Animals; D008297:Male; D008437:Maxilla / Q000378:metabolism*; D008963:Molar / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000378:metabolism* / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000378:metabolism*
chemical_list: D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C507968:hemokinin-1; D013373:Substance P