Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.
Animals ; Calcitonin/*pharmacology ; Cell Line ; Connective Tissue Growth Factor/*genetics/metabolism ; Female ; Kidney Tubules, Proximal/*enzymology/metabolism ; *MAP Kinase Signaling System ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Phosphorylation ; Swine

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.
Animals ; Calcitonin/*pharmacology ; Cell Line ; Connective Tissue Growth Factor/*genetics/metabolism ; Female ; Kidney Tubules, Proximal/*enzymology/metabolism ; *MAP Kinase Signaling System ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3/*metabolism ; Phosphorylation ; Swine

Since hand deformities in rheumatoid arthritis (RA) are relatively not very painful, the worsening of the deformities often goes unnoticed and the functional impairment progresses irreversibly. Herein, we report a case of boutonnière deformity of the left middle and ring fingers treated with rehabilitation since an early stage. The patient was a 58-year-old woman who was referred to our hospital due to joint pain in the fingers and feet, following which a diagnosis of RA as made；however, she could not be administered methotrexate due to complications. PIP joint deformity of the left middle and ring fingers developed later. The middle finger was in -50-degree extension and difficult to correct passively, while the ring finger was in -35-degree extension and correctable. Surgery for the left middle finger was proposed based on the diagnosis of boutonnière deformity；however, consent was not obtained. After a steroid injection in the painful middle finger, she was managed using a Capener splint and ROM exercises with finger stretching. The symptoms improved five months following the rehabilitation intervention. Nalebuff et al. classified the severity of the boutonnière deformity based on the limited PIP joint extension and recommended treatment accordingly. In this case, surgical treatment was believed to be required；however, since the patient refused surgery, conservative treatment was chosen. Although the extension was severe, there was little joint destruction, due to which the symptoms improved with early and active intervention. Orthotic treatment and occupational therapy were effective in improving ADL.

Since hand deformities in rheumatoid arthritis (RA) are relatively not very painful, the worsening of the deformities often goes unnoticed and the functional impairment progresses irreversibly. Herein, we report a case of boutonnière deformity of the left middle and ring fingers treated with rehabilitation since an early stage. The patient was a 58-year-old woman who was referred to our hospital due to joint pain in the fingers and feet, following which a diagnosis of RA as made；however, she could not be administered methotrexate due to complications. PIP joint deformity of the left middle and ring fingers developed later. The middle finger was in -50-degree extension and difficult to correct passively, while the ring finger was in -35-degree extension and correctable. Surgery for the left middle finger was proposed based on the diagnosis of boutonnière deformity；however, consent was not obtained. After a steroid injection in the painful middle finger, she was managed using a Capener splint and ROM exercises with finger stretching. The symptoms improved five months following the rehabilitation intervention. Nalebuff et al. classified the severity of the boutonnière deformity based on the limited PIP joint extension and recommended treatment accordingly. In this case, surgical treatment was believed to be required；however, since the patient refused surgery, conservative treatment was chosen. Although the extension was severe, there was little joint destruction, due to which the symptoms improved with early and active intervention. Orthotic treatment and occupational therapy were effective in improving ADL.