Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo.
Lactoferrin is an iron-binding glycoprotein present in epithelial secretions, such as milk, and in the secondary granules of neutrophils. We found it to be present in fractions of milk protein that stimulated osteoblast growth, so we assessed its effects on bone cell function. Lactoferrin produced large, dose-related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast-like cells, at physiological concentrations (1-100 microg/ml). Maximal stimulation was 5-fold above control. Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50-70%. Similarly, lactoferrin stimulated proliferation of primary chondrocytes. Purified, recombinant, human, or bovine lactoferrins had similar potencies. In mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and was completely arrested by lactoferrin, 100 microg/ml, associated with decreased expression of receptor activator of nuclear factor-kappaB ligand. In contrast, lactoferrin had no effect on bone resorption by isolated mature osteoclasts. Lactoferrin was administered over calvariae of adult mice for 5 d. New bone formation, assessed using fluorochrome labels, was increased 4-fold by a 4-mg dose of lactoferrin. Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth.
Cornish
Jillian
J
Department of Medicine, University of Auckland, Private Bag 92019, Auckland 1001, New Zealand. j.cornish@auckland.ac.nz.
Callon
Karen E
KE
Naot
Dorit
D
Palmano
Kate P
KP
Banovic
Tatjana
T
Bava
Usha
U
Watson
Maureen
M
Lin
Jian-Ming
JM
Tong
P C
PC
Chen
Qi
Q
Chan
Vincent A
VA
Reid
Helen E
HE
Fazzalari
Nick
N
Baker
Heather M
HM
Baker
Edward N
EN
Haggarty
Neill W
NW
Grey
Andrew B
AB
Reid
Ian R
IR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002356:Cartilage / Q000166:cytology / Q000254:growth & development; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D006224:Cricetinae; D006801:Humans; D007668:Kidney / Q000166:cytology; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008892:Milk / Q000737:chemistry; D008895:Milk, Human / Q000737:chemistry; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D051381:Rats; D012886:Skull / Q000166:cytology / Q000254:growth & development
D007781:Lactoferrin