Tail-suspended mice lacking calponin H1 experience decreased bone loss.
Calponin h1 (CNh1) is an actin-binding protein originally isolated from vascular smooth muscle and has been reported to suppress bone formation. We are therefore curious how CNh1 is involved in bone loss that is caused by space flight in microgravity. We assessed the effects of tail suspension (TS) in C57BL/6J wild (CN+/+) and CNh1-deleted (CN-/-) mice to elucidate the role of CNh1 in bone loss under weightless conditions. Bone mineral density (BMD) of tibiae was measured by single energy X-ray absorptiometry, and bone volume fraction (BV/TV), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were measured by bone histomorphometry. BMD, BV/TV, MAR, and BFR/BS were lower in CN+/+ mice with TS than in those without. In the CN-/- group, however, the decrease in each of these parameters by TS was ameliorated. Decreases in serum osteocalcin levels by TS in CN+/+ mice were attenuated in CN-/- mice. Furthermore, urinary deoxypyridinolin (DPD), an indicator of bone resorption, was increased in CN+/+ mice following TS, but not in CN-/- mice. In transfection experiments, the degree of induction of bone formation markers, alkaline phosphatase (ALP) activity and bone morphogenetic protein (BMP)-4 mRNA expression, under stimulation with BMP-2, was lower in MC3T3-E1 mouse osteoblast-like cells expressing CNh1 than that in mock transfected cells. Notably, the BMP-2-induced ALP activity was decreased by CNh1 expression, which was partially rescued by treatment with the Rho kinase inhibitor Y27632. Taken together, these results indicate that CNh1 is responsible for weightlessness-induced bone loss in part through Rho signaling pathway.
Yotsumoto
Naoki
N
Shinkatsushika Hospital, Tokyo, Japan.
Takeoka
Michiko
M
Yokoyama
Minesuke
M
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002454:Cell Differentiation; D019417:Hindlimb Suspension; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D015398:Signal Transduction; D013977:Tibia / Q000378:metabolism; D014162:Transfection; D014965:X-Rays; D000096985:Calponins
D055396:Bone Morphogenetic Protein 2; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D000096985:Calponins