title: Bromocriptine modulates the expression of PTHrP receptor, Indian hedgehog, and Runx2 proteins in the growth plate of lactating rats.
abstract: In lactating rats, the endochondral bone growth is markedly enhanced, leading to the lengthening of long bone. This lactation-induced bone elongation could be abolished by a dopaminergic D2 receptor agonist bromocriptine, but how bromocriptine altered the expression of major chondroregulatory proteins in the growth plate cartilage was elusive. Here, we performed a quantitative immunohistochemical analysis to determine the expression of various peptides and transcription factors known to control the growth plate chondrocyte proliferation and differentiation [i.e., parathyroid hormone-related protein (PTHrP), PTHrP receptor, Indian hedgehog (Ihh), and runt-related transcription factor 2 (Runx2)], in bromocriptine-treated lactating rats. The results showed that bromocriptine markedly increased Ihh expression in hypertrophic chondrocytes during early and mid-lactation, while the expression of PTHrP receptor, but not its ligand PTHrP, was upregulated in the proliferative and hypertrophic zones during mid and late lactation. In contrast, the expression of Runx2, an important transcription factor for chondrocyte differentiation, was suppressed in the hypertrophic chondrocytes of bromocriptine-treated rats. In conclusion, bromocriptine increased Ihh and PTHrP receptor expressions and decreased Runx2 expression, which might, in turn, enhance chondrocyte proliferation and delay chondrocyte hypertrophy, thereby slowing down endochondral bone growth. This finding could explain how bromocriptine compromised the lactation-induced bone elongation.
authors.affiliation: Office of Academic Management, Faculty of Allied Health Sciences, Burapha University, Chonburi, Thailand.
authors.forename: Kannikar
authors.initials: K
authors.lastname: Wongdee
authors.forename: Natchayaporn
authors.initials: N
authors.lastname: Thonapan
authors.forename: Wasana
authors.initials: W
authors.lastname: Saengamnart
authors.forename: Nateetip
authors.initials: N
authors.lastname: Krishnamra
authors.forename: Narattaphol
authors.initials: N
authors.lastname: Charoenphandhu
mesh_terms: D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D005260:Female; D006132:Growth Plate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007774:Lactation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism*; D013977:Tibia / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; C550919:Ihh protein, rat; D044168:Receptor, Parathyroid Hormone, Type 1; D001971:Bromocriptine