Chemical structure effects on bone response to mechanical loading

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S390
Author(s):  
Peizhi Zhu ◽  
Jiadi Xu ◽  
Michael Morris ◽  
David Kohn ◽  
Ayyalusamy Ramamoorthy
2009 ◽  
Vol 96 (3) ◽  
pp. 409a
Author(s):  
Peizhi Zhu ◽  
Jiadi Xu ◽  
Michael D. Morris ◽  
Nadder Sahar ◽  
David H. Kohn ◽  
...  

2005 ◽  
Vol 99 (5) ◽  
pp. 1951-1957 ◽  
Author(s):  
Chandrasekhar Kesavan ◽  
Subburaman Mohan ◽  
Susanna Oberholtzer ◽  
Jon E. Wergedal ◽  
David J. Baylink

Our goal is to evaluate skeletal anabolic response to mechanical loading in different age groups of C57B1/6J (B6) and C3H/HeJ (C3H) mice with variable loads using bone size, bone mineral density (BMD), and gene expression changes as end points. Loads of 6–9 N were applied at 2 Hz for 36 cycles for 12 days on the tibia of 10-wk-old female B6 and C3H mice. Effects of a 9-N load on 10-, 16-, and 36-wk-old C3H mice were also studied. Changes in bone parameters were measured using peripheral quantitative computed tomography, and gene expression was determined by real-time PCR. Total volumetric BMD was increased by 5 and 15%, respectively, with 8- and 9-N loads in the B6, but not the C3H, mice. Increases of 20 and 12% in periosteal circumference were reflected by dramatic 44 and 26% increases in total area in B6 and C3H mice, respectively. The bone response to bending showed no difference in the three age groups of B6 and C3H mice. At 2 days, mechanical loading resulted in significant downregulation in expression of bone resorption (BR), but not bone formation (BF) marker genes. At 4 and 8 days of loading, expression of BF marker genes (type I collagen, alkaline phosphatase, osteocalcin, and bone sialoprotein) was increased two- to threefold and expression of BR marker genes (matrix metalloproteinase-9 and thrombin receptor-activating peptide) was decreased two- to fivefold. Although expression of BF marker genes was upregulated four- to eightfold at 12 days of training, expression of BR marker genes was upregulated seven- to ninefold. Four-point bending caused significantly greater changes in expression of BF and BR marker genes in bones of the B6 than the C3H mice. We conclude that mechanical loading-induced molecular pathways are activated to a greater extent in the B6 than in the C3H mice, resulting in a higher anabolic response in the B6 mice.


2014 ◽  
Vol 117 (11) ◽  
pp. 1349-1355 ◽  
Author(s):  
Sibyl N. Swift ◽  
Joshua M. Swift ◽  
Susan A. Bloomfield

Estrogen receptor-α (ER-α) is an important mediator of the bone response to mechanical loading. We sought to determine whether restricting dietary energy intake by 40% limits the bone formation rate (BFR) response to mechanical loading (LOAD) by downregulating ER-α-expressing osteocytes, or osteoblasts, or both. Female rats ( n = 48, 7 mo old) were randomized to ADLIB-SHAM and ADLIB-LOAD groups fed AIN-93M purified diet ad libitum or to ER40-SHAM and ER40-LOAD groups fed modified AIN-93M with 40% less energy (100% of all other nutrients). After 12 wk, LOAD rats were subjected to a muscle contraction protocol three times every third day. ER40 produced lower proximal tibia bone volume (−22%), trabecular thickness (−14%), and higher trabecular separation (+127%) in SHAM but not LOAD rats. ER40 rats exhibited reductions in mineral apposition rate, but not percent mineralizing surface or BFR. LOAD induced similar relative increases in these kinetic measures of osteoblast activity/recruitment in both diet groups., but absolute values for ER40 LOAD rats were lower vs. ADLIB-LOAD. There were fourfold and eightfold increases in proportion of estrogen receptor-α protein-positive osteoblast and osteocytes, respectively, in LOAD vs. SHAM rats, with no effect of ER40. These data suggest that a brief period of mechanical loading significantly affects estrogen receptor-α in cancellous bone osteoblasts and osteocytes. Chronic energy restriction does result in lower absolute values in indices of osteoblast activity after mechanical loading, but not by a smaller increment relative to unloaded bones; this change is not explained by an associated downregulation of ER-α in osteoblasts or osteocytes.


1998 ◽  
Vol 63 (5) ◽  
pp. 442-449 ◽  
Author(s):  
M. P. Akhter ◽  
D. M. Cullen ◽  
E. A. Pedersen ◽  
D. B. Kimmel ◽  
R. R. Recker

2001 ◽  
Vol 19 (2) ◽  
pp. 328-336 ◽  
Author(s):  
Eva Samnegård ◽  
Diane M. Cullen ◽  
Mohammed P. Akhter ◽  
Donald B. Kimmel

Bone ◽  
2004 ◽  
Vol 35 (4) ◽  
pp. 948-956 ◽  
Author(s):  
Yasuhiro Kameyama ◽  
Hiroshi Hagino ◽  
Toru Okano ◽  
Makoto Enokida ◽  
Satoru Fukata ◽  
...  

2017 ◽  
Vol 29 (4) ◽  
pp. 385-395 ◽  
Author(s):  
Keren E. Dittmer ◽  
Elwyn C. Firth

Bone, despite its relatively inert appearance, is a tissue that is capable of adapting to its environment. Wolff’s law, first described in the 19th century, describes the ability of bone to change structure depending on the mechanical forces applied to it. The mechanostat model extended this principle and suggested that the amount of strain a bone detects depends on bone strength and the amount of muscle force applied to the bone. Experimental studies have found that low-magnitude, high-frequency mechanical loading is considered to be the most effective at increasing bone formation. The osteocyte is considered to be the master regulator of the bone response to mechanical loading. Deformation of bone matrix by mechanical loading is thought to result in interstitial fluid flow within the lacunar–canalicular system, which may activate osteocyte mechanosensors, leading to changes in osteocyte gene expression and ultimately increased bone formation and decreased bone resorption. However, repetitive strain applied to bone can result in microcracks, which may propagate and coalesce, and if not repaired predispose to catastrophic fracture. Osteocytes are a key component in this process, whereby apoptotic osteocytes in an area of microdamage promote targeted remodeling of the damaged bone. If fractures do occur, fracture repair can be divided into 2 types: primary and secondary healing. Secondary fracture repair is the most common and is a multistage process consisting of hematoma formation and acute inflammation, callus formation, and finally remodeling, whereby bone may return to its original form.


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