Cyclic mechanical strain regulates the PTHrP expression in cultured chondrocytes via activation of the Ca2+ channel.
The association between mechanical stimulation and chondrocyte homeostasis has been reported. However, the participation of PTHrP (parathyroid-hormone-related protein) in the mechano-regulation of chondrocyte metabolism remains unclear. We determined whether mechanical stimulation of chondrocytes induces the expression of PTHrP and, further, whether the mechano-modulation of PTHrP is dependent on the maturational status of chondrocytes. Cyclic mechanical strain was applied to rat growth plate chondrocytes at the proliferating, matrix-forming, and hypertrophic stages at 30 cycles/min. Cyclic mechanical strain significantly increased PTHrP mRNA levels in chondrocytes at the proliferating and matrix-forming stages only. The induction of PTHrP was dependent on loading magnitude at the proliferating stage. Using specific ion channel blockers, we determined that mechano-induction of PTHrP was inhibited by nifedipine, a Ca2+ channel blocker. These results suggest that mechanical induction of PTHrP possibly provides the environment for greater chondrocyte replication and matrix formation that would subsequently affect cartilage formation.
Tanaka
N
N
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8553, Japan.
Ohno
S
S
Honda
K
K
Tanimoto
K
K
Doi
T
T
Ohno-Nakahara
M
M
Tafolla
E
E
Kapila
S
S
Tanne
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006132:Growth Plate / Q000166:cytology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis*; D010812:Physical Stimulation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016326:Extracellular Matrix Proteins; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D009543:Nifedipine