Bone adaptation requires oestrogen receptor-α

Lee, Karla; Jessop, Helen; Suswillo, Rosemary F. L.; Zaman, Gul; Lanyon, Lance E.

doi:10.1038/424389a

Cited by 306 publications

(217 citation statements)

References 9 publications

Supporting

Mentioning

195

Contrasting

Unclassified

Order By: Relevance

“…A number of in vivo animal models have been developed to study the effect of specific components of an applied mechanical load on bone tissue including the following examples: compression of the functionally isolated turkey ulna (Rubin and Lanyon, 1984a), bending of the rat and mouse ulna (Mosley et al, 1997) and tibia , and 4-point bending to rat tibia (Lee et al, 2003). Distinct parameters of the applied loads can be correlated to changes in bone morphology (Rubin and Lanyon, 1985;Rubin et al, 1996Rubin et al, , 2001aSrinivasan et al, 2002) as well as changes in gene and protein expression (Sun et al, 1995;Rawlinson et al, 1998;Lee et al, 2003;Judex et al, 2004) At the level of small volumes of tissue, all loads and bending moments resolve into strain, or change in length of a material from its original length.…”

Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 99%

“…Distinct parameters of the applied loads can be correlated to changes in bone morphology (Rubin and Lanyon, 1985;Rubin et al, 1996Rubin et al, , 2001aSrinivasan et al, 2002) as well as changes in gene and protein expression (Sun et al, 1995;Rawlinson et al, 1998;Lee et al, 2003;Judex et al, 2004) At the level of small volumes of tissue, all loads and bending moments resolve into strain, or change in length of a material from its original length. During vigorous activities, peak strain magnitudes measured in the load-bearing regions of the skeleton of adult species, including horse, human, lizard, sheep, goat, etc., are all remarkably similar ranging from 2000 to 3500 microstrain (note 1000 microstrain = 0.1% change in length) (Rubin and Lanyon, 1984b).…”

Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 99%

See 1 more Smart Citation

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

403

303

View full text Add to dashboard Cite

Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

show abstract

Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 99%

Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

403

303

View full text Add to dashboard Cite

show abstract

“…In the literature, a few studies support ERα's involvement in the adaptive response of osteoblasts to mechanical strain [47][48][49][50] . ERα-/-mice produced three times less new cortical bone in response to the same mechanical stimulus as their ERα+/+ littermates [47,48] .…”

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentmentioning

confidence: 99%

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Xing

Wang

et al. 2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats. Methods: Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10 -7 or 10 -4 mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using realtime PCR, and ER silencing was performed. Results: At both the low-and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment. Conclusion: In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.

show abstract

“…39 ESR1, which encodes the estrogen receptor, is associated with changes in the bone mineral density and has a major role in osteoporosis and bone's osteogenic response. [40][41][42] Cohesin is enriched in promoters of estrogen-responsive genes, pointing out a possible collaboration between it and ESR1. Furthermore, depletion of the cohesin subunit SMC3 significantly impaired the estrogenregulated transcriptome.…”

Section: Possible Involvement Of Smcs In Molecular Pathways Of Bone Dmentioning

confidence: 99%

“…Cohesin binds chromatin and regulates gene expression in response to estrogen [40][41][42]43 TNF-a An inflammatory cytokine involved in immunity and inflammation…”

Section: Esr1mentioning

confidence: 99%

Structural maintenance of chromosome complexes and bone development: the beginning of a wonderful relationship?

Cohen-Zinder¹,

Karasik

Onn

2013

BoneKEy Reports

View full text Add to dashboard Cite

Bone development depends on environmental, nutritional and hormonal factors. Yet, an ordered and timed activation of genes and their associated molecular pathways are central for the growth and development of healthy bones. The correct expression of genes depends on both cis-and trans-regulatory elements. Of these, the elusive role of chromatin ultrastructure is just beginning to become appreciated. Changes in the higher-order structure of chromatin are affecting the expression of genes in response to intrinsic and environmental signals. Cohesin and condensin are members of the structural maintenance of chromosome (SMC) family of protein complexes, which mediate higher-order chromatin structure by tethering distinct regions of chromatin either inter-or intra-molecularly. In recent years, SMCs had been identified for their function in the regulation of gene expression and developmental processes, whereas malfunction of cohesin or condensin has an impact on human health. However, little is known about the specific roles of SMC complexes in bone development and their possible effect on bone health. Here, we review studies that suggest an intimate link between SMCs and bone development, as well as a plausible effect, direct or indirect, on the bone health. We describe genetic syndromes associated with SMCs with distinctive bone phenotypes and identify links between SMCs and bone-related molecular pathways. Future studies of the relationship between SMCs and bone development will reveal new understandings of both the cellular and molecular roles of SMC complexes and provide new insights into the growth and developmental processes in the bone.

show abstract

Bone adaptation requires oestrogen receptor-α

Cited by 306 publications

References 9 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Structural maintenance of chromosome complexes and bone development: the beginning of a wonderful relationship?

Contact Info

Product

Resources

About