ABSTRACT
no abstract available.
ABSTRACT
Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDXMS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.
ABSTRACT
Sclerostin (SOST), a regulator of bone formation in osteocytes, inhibits the canonical Wnt signaling by interacting with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent Wnt binding. Loss-of-function mutations of the SOST gene caused massive bone outgrowth and SOST-null mouse exhibited a high bone density phenotype. Therefore, SOST has been suggested as a promising therapeutic target for osteoporosis. A few previous studies with X-ray crystallography identified the binding interfaces between LRP6 and SOST, but there are limitations in these studies as they used truncated SOST protein or SOST peptide. Here, we analyzed the conformational dynamics of SOST-LRP6 E1E2 complex using hydrogen/deuterium exchange mass spectrometry (HDX-MS). We examined the effect of the C-terminal tail of SOST on LRP6 conformation upon complex formation. HDXMS analysis suggested a new potential binding interface for the C-terminal region of SOST that was missing from the previous crystal structure of the SOST-LRP6 E1E2 complex.
ABSTRACT
Whole-body vibration exercise (WBVe) can provide proper somatosensory stimulation and improve muscle strength in stroke patients. This study investigated the effects of WBVe on gait function and cortical activity in patients with chronic stroke. Thirty stroke patients were randomly assigned to either the WBVe or the control group. The WBVe group received the vibration in a half-squat position for 5 minutes at an intensity of 20 Hz. The control group kept the same posture but did not receive the vibration. Cortical activity was investigated using functional near-infrared spectroscopy (fNIRS). Gait function was assessed by a 10-m walk test (10MWT), a timed up and go (TUG) test, a Fugl-Meyer Assessment, and a Tinetti Performance-Oriented Mobility Assessment (TPOMA). In group analysis of the fNIRS data, oxygenated hemoglobin concentration was significantly increased in the ipsilesional supplementary motor area, bilateral sensorimotor cortex, and contralesional prefrontal cortex in the WBVe group compared to the control group (p < 0.05). Functional assessment demonstrated a significant interaction between time and group for the 10MWT and TUG test, suggesting that the WBVe group demonstrated meaningful improvement after intervention (p < 0.05). These results suggested that WBVe modulated the cerebral cortical activities and resulted in improvement of gait function in chronic stroke patients.
ABSTRACT
Whole-body vibration exercise (WBVe) can provide proper somatosensory stimulation and improve muscle strength in stroke patients. This study investigated the effects of WBVe on gait function and cortical activity in patients with chronic stroke. Thirty stroke patients were randomly assigned to either the WBVe or the control group. The WBVe group received the vibration in a half-squat position for 5 minutes at an intensity of 20 Hz. The control group kept the same posture but did not receive the vibration. Cortical activity was investigated using functional near-infrared spectroscopy (fNIRS). Gait function was assessed by a 10-m walk test (10MWT), a timed up and go (TUG) test, a Fugl-Meyer Assessment, and a Tinetti Performance-Oriented Mobility Assessment (TPOMA). In group analysis of the fNIRS data, oxygenated hemoglobin concentration was significantly increased in the ipsilesional supplementary motor area, bilateral sensorimotor cortex, and contralesional prefrontal cortex in the WBVe group compared to the control group (p < 0.05). Functional assessment demonstrated a significant interaction between time and group for the 10MWT and TUG test, suggesting that the WBVe group demonstrated meaningful improvement after intervention (p < 0.05). These results suggested that WBVe modulated the cerebral cortical activities and resulted in improvement of gait function in chronic stroke patients.