Osteoporosis in MCHR1-deficient mice.
It is well recognized that the hypothalamus is of central importance in the regulation of food intake and fat mass. Recent studies indicate that it also plays an important role in the regulation of bone mass. Melanin concentrating hormone (MCH) is highly expressed in the hypothalamus and has been implicated in regulation of energy homeostasis. We developed MCHR1 inactivated mice to evaluate the physiological role of this receptor. Interestingly, the MCHR1(-/-) mice have osteoporosis, caused by a reduction in the cortical bone mass, while the amount of trabecular bone is unaffected. The reduction in cortical bone mass is due to decreased cortical thickness. Serum levels of c-telopeptide, a marker of bone resorption, are increased in MCHR1(-/-) mice, indicating that the MCHR1(-/-) mice have a high bone turnover osteoporosis. In conclusion, the MCHR1(-/-) mice have osteoporosis, indicating that MCHR1-signalling is involved in a tonic stimulation of bone mass.
Bohlooly-Y
Mohammad
M
AstraZeneca Transgenics and Comparative Genomics Centre, AstraZeneca R&D, Mölndal, Sweden.
Mahlapuu
Margit
M
Andersén
Harriet
H
Astrand
Annika
A
Hjorth
Stephan
S
Svensson
Lennart
L
Törnell
Jan
J
Snaith
Michael R
MR
Morgan
David G
DG
Ohlsson
Claes
C
D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology; D001862:Bone Resorption / Q000097:blood; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D005260:Female; D005269:Femur / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D040461:Gene Components; D015870:Gene Expression; D007028:Hypothalamic Hormones / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000097:blood; D010907:Pituitary Hormones / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011979:Receptors, Pituitary Hormone / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D014018:Tissue Distribution
D015415:Biomarkers; D024042:Collagen Type I; D007028:Hypothalamic Hormones; D008543:Melanins; D010455:Peptides; D010907:Pituitary Hormones; D012333:RNA, Messenger; D011979:Receptors, Pituitary Hormone; C052929:collagen type I trimeric cross-linked peptide; C092274:melanin-concentrating hormone receptor; D015675:Osteocalcin; C019463:melanin-concentrating hormone; D003094:Collagen