Inhibition of Osteoclastogenesis by Mechanically Loaded Osteocytes: Involvement of MEPE

In regions of high bone loading, the mechanoresponsive osteocytes inhibit osteoclastic bone resorption by producing signaling molecules. One possible candidate is matrix extracellular phosphoglycoprotein (MEPE) because acidic serine- and aspartate-rich MEPE-associated motif peptides upregulate osteoprotegerin (OPG) gene expression, a negative regulator of osteoclastogenesis. These peptides are cleaved from MEPE when relatively more MEPE than PHEX (phosphate-regulating gene with homology to endopeptidases on the X chromosome) is present. We investigated whether mechanical loading of osteocytes affects osteocyte-stimulated osteoclastogenesis by involvement of MEPE. MLO-Y4 osteocytes were mechanically loaded by 1-h pulsating fluid flow (PFF; 0.7 ± 0.3 Pa, 5 Hz) or kept under static control conditions. Recombinant MEPE (0.05, 0.5, or 5 μg/ml) was added to some static cultures. Mouse bone marrow cells were seeded on top of the osteocytes to determine osteoclastogenesis. Gene expression of MEPE, PHEX, receptor activator of nuclear factor kappa-B ligand (RANKL), and OPG by osteocytes was determined after PFF. Osteocytes supported osteoclast formation under static control conditions. Both PFF and recombinant MEPE inhibited osteocyte-stimulated osteoclastogenesis. PFF upregulated MEPE gene expression by 2.5-fold, but not PHEX expression. PFF decreased the RANKL/OPG ratio at 1-h PFF treatment. Our data suggest that mechanical loading induces changes in gene expression by osteocytes, which likely contributes to the inhibition of osteoclastogenesis after mechanical loading of bone. Because mechanical loading upregulated gene expression of MEPE but not PHEX, possibly resulting in the upregulation of OPG gene expression, we speculate that MEPE is a soluble factor involved in the inhibition of osteoclastogenesis by osteocytes

Mechanical Strain Regulates Osteoblast Proliferation through Integrin-Mediated ERK Activation

Mechanical strain plays a critical role in the proliferation, differentiation and maturation of bone cells. As mechanical receptor cells, osteoblasts perceive and respond to stress force, such as those associated with compression, strain and shear stress. However, the underlying molecular mechanisms of this process remain unclear. Using a four-point bending device, mouse MC3T3-E1 cells was exposed to mechanical tensile strain. Cell proliferation was determined to be most efficient when stimulated once a day by mechanical strain at a frequency of 0.5 Hz and intensities of 2500 µε with once a day, and a periodicity of 1 h/day for 3 days. The applied mechanical strain resulted in the altered expression of 1992 genes, 41 of which are involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of ERK by mechanical strain promoted cell proliferation and inactivation of ERK by PD98059 suppressed proliferation, confirming that ERK plays an important role in the response to mechanical strain. Furthermore, the membrane-associated receptors integrin β1 and integrin β5 were determined to regulate ERK activity and the proliferation of mechanical strain-treated MC3T3-E1 cells in opposite ways. The knockdown of integrin β1 led to the inhibition of ERK activity and cell proliferation, whereas the knockdown of integrin β5 led to the enhancement of both processes. This study proposes a novel mechanism by which mechanical strain regulates bone growth and remodeling

Do General Dental Practitioners have a role in identifying dental patients with mental health problems.

Objective To examine whether general dental practitioners regard themselves as having a role in identifying dental patients with mental health problems.Method Telephone interviews were conducted with, and postal questionnaires were sent to, a random sample (n = 94) of general dental practitioners on Health Authority lists within the Mersey Region. A total of 84 general dental practitioners responded, resulting in an 89% response rate.Results The majority of general dental practitioners had encountered patients with mental health problems (78% of interviewees, 56% of questionnaire responders). However, nearly half of the interviewees (46%) do not refer patients with mental health problems. When referrals to dental specialists were made, they tended to be regarding a physical manifestation rather than a psychological one. The majority of interviewees and questionnaire responders (55% and 82% respectively) expressed a 'positive' response to the development of a referral role. Nevertheless, there were some reservations concerning the practicalities of its development and implementation.Conclusion The majority of general dental practitioners consider a role in identifying patients with possible mental health problems. This role might include, being able to identify patients with undiagnosed mental health problems, and being aware of dental conditions which may be caused by mental health problems. To achieve this, inter-professional co-operation between general dental practitioners and other health professionals requires development.</p

Physical activity in the post-pubertal period is associated with maintenance of pre-pubertal high bone density - a 5-year follow-up

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To evaluate the association between physical activity (PA) and skeletal growth in girls during adolescence. DESIGN: A 5-year, observational, population-based study (Reykjavik, Iceland). Subjects: Seventy-eight Caucasian girls, mean age 13.4+/-1.0 (mean+/-SD) years at baseline. METHODS: Bone mineral density (BMD, g/cm2) and bone width (cm) were measured in the forearm by single-photon absorptiometry at baseline and with dual-energy X-ray absorptiometry after 3 and 5 years, when lumbar spine, femoral neck (FN) and total body were also evaluated. Half of the physically active girls were compared with the other half of less active girls. RESULTS: BMD in physically active girls was higher in the forearm at both baseline (P=0.001) and after 5 years (P=0.04) in comparison with less active girls. BMD was higher for the total body (P=0.0001), spine L2-L4 (P=0.02) and FN (P=0.002) in the active girls at age 18. The accrual of forearm BMD and bone width from age 13 to 18 was no different when comparing the two groups. CONCLUSIONS: Pre-pubertal PA is associated with high BMD at age 13 and continued PA is associated with maintenance of high BMD until age 18