How does Mechanical Loading Make Bone Microstructure: Modeling vs. Remodeling
|
摘要
Bone modeling and remodeling are governed by distinct biochemical processes that may hold unique opportunities for optimizing bone mass~([1,2]).Remodeling refers to the coupled resorption and subsequent formation on the bone surface,while modeling represents uncoupled formation or resorption.Mechanical loading is known to improve bone mass,though whether this occurs through modeling or remodeling(or by some combination)is unclear.Dynamic in vivo morphometry utilizing high resolution micro-CT and image registration has only recently become feasible and thus holds an untapped and expanding potential for understanding bone metabolism by quantifying and localizing formation/resorption and modeling/remodeling events.16-week-old mice were given 2 baseline weekly micro-CT scans of both tibiae prior to the initiation of daily unilateral loading(contralateral limb for nonloaded control).Weekly scanning and daily loading continued for 5 weeks.Registered images for each mouse in a global coordinate system revealed the time course of each voxel,and changes in bone mass were quantified as modeling or remodeling starting at the onset of loading.In cortical bone,after an initial response to loading in both regimes,modeling emerged as the dominant response.Loading effects were largest in areas of mechanical significance.For example,anabolic modeling on the periosteal surface of the half of the tibia in compression under axial load presented a strong effect of loading,whereas the same measure on the endosteal surface in the area in tension showed no difference.Similarly,in trabecular bone anabolic modeling was significantly increased with loading on trabecular plates but not rods(plates have been shown to be the major contributor to overall bone strength).The catabolic modeling response on the endosteal surface showed an interesting transition over time.Loading initially led to a significant suppression of catabolic modeling,but over time increased it to levels significantly beyond that of nonloaded controls.
Bone modeling and remodeling are governed by distinct biochemical processes that may hold unique opportunities for optimizing bone mass~([1,2]).Remodeling refers to the coupled resorption and subsequent formation on the bone surface,while modeling represents uncoupled formation or resorption.Mechanical loading is known to improve bone mass,though whether this occurs through modeling or remodeling(or by some combination)is unclear.Dynamic in vivo morphometry utilizing high resolution micro-CT and image registration has only recently become feasible and thus holds an untapped and expanding potential for understanding bone metabolism by quantifying and localizing formation/resorption and modeling/remodeling events.16-week-old mice were given 2 baseline weekly micro-CT scans of both tibiae prior to the initiation of daily unilateral loading(contralateral limb for nonloaded control).Weekly scanning and daily loading continued for 5 weeks.Registered images for each mouse in a global coordinate system revealed the time course of each voxel,and changes in bone mass were quantified as modeling or remodeling starting at the onset of loading.In cortical bone,after an initial response to loading in both regimes,modeling emerged as the dominant response.Loading effects were largest in areas of mechanical significance.For example,anabolic modeling on the periosteal surface of the half of the tibia in compression under axial load presented a strong effect of loading,whereas the same measure on the endosteal surface in the area in tension showed no difference.Similarly,in trabecular bone anabolic modeling was significantly increased with loading on trabecular plates but not rods(plates have been shown to be the major contributor to overall bone strength).The catabolic modeling response on the endosteal surface showed an interesting transition over time.Loading initially led to a significant suppression of catabolic modeling,but over time increased it to levels significantly beyond that of nonloaded controls.
Bone modeling and remodeling are governed by distinct biochemical processes that may hold unique opportunities for optimizing bone mass~([1,2]).Remodeling refers to the coupled resorption and subsequent formation on the bone surface,while modeling represents uncoupled formation or resorption.Mechanical loading is known to improve bone mass,though whether this occurs through modeling or remodeling(or by some combination)is unclear.Dynamic in vivo morphometry utilizing high resolution micro-CT and image registration has only recently become feasible and thus holds an untapped and expanding potential for understanding bone metabolism by quantifying and localizing formation/resorption and modeling/remodeling events.16-week-old mice were given 2 baseline weekly micro-CT scans of both tibiae prior to the initiation of daily unilateral loading(contralateral limb for nonloaded control).Weekly scanning and daily loading continued for 5 weeks.Registered images for each mouse in a global coordinate system revealed the time course of each voxel,and changes in bone mass were quantified as modeling or remodeling starting at the onset of loading.In cortical bone,after an initial response to loading in both regimes,modeling emerged as the dominant response.Loading effects were largest in areas of mechanical significance.For example,anabolic modeling on the periosteal surface of the half of the tibia in compression under axial load presented a strong effect of loading,whereas the same measure on the endosteal surface in the area in tension showed no difference.Similarly,in trabecular bone anabolic modeling was significantly increased with loading on trabecular plates but not rods(plates have been shown to be the major contributor to overall bone strength).The catabolic modeling response on the endosteal surface showed an interesting transition over time.Loading initially led to a significant suppression of catabolic modeling,but over time increased it to levels significantly beyond that of nonloaded controls.
引文
[1] Tang Y.,et al.,2009,“TGF-β1-induced Migration of Bone Mesenchymal Stem Cells Couples Bone Resorption and Formation,”Nature Medicine,15(7),pp. 757-765.
[2] Hui X.,et al.,2009,“PDGF-BB secreted by preosteoclasts induces CD31hiEmcnhivessel subtype in coupling osteogenesis,”Nature Medicine,20(11),pp. 1270-1278.
[2] Hui X.,et al.,2009,“PDGF-BB secreted by preosteoclasts induces CD31hiEmcnhivessel subtype in coupling osteogenesis,”Nature Medicine,20(11),pp. 1270-1278.