The interaction of mechanical strain and sex hormones in bone's adaptive responses to load-bearing

Abstract

An experimental model of rat ulna was established to study the effects on residential bone cells of mechanical strain, prostaglandins (PGs), sex hormones and their combination in vitro. The shafts of ulnae from 110 gm rats were cultured. After a period of 5 hours pre-incubation, one of each pair of bones was either loaded cyclically (500 gm, 1 Hz, 8 min) to produce physiological strains, or treated with exogenous PGE₂ or PGI₂(10^-6 M), in the presence or absence of 10^-8 M 17<IMG WIDTH=9 HEIGHT=24 ALIGN=MIDDLE SRC="/maths/beta.gif">-oestradiol (E2) or 5<IMG WIDTH=7 HEIGHT=7 ALIGN=BOTTOM SRC="/maths/alpha.gif">-dihydrotestosterone (DHT).

Loading, prostaglandin E₂ (PGE₂) and prostacyclin (PGI₂) stimulated almost immediate increases in glucose 6-dehydrogenase (G6PD) activity in osteocytes and osteoblasts. This increase was uniform throughout the section with exogenous PGs but was related to local strain magnitude in loading. Elevated G6PD levels in response to loading and PGI₂ persisted for 18 hours, by which time alkaline phosphatase (ALP) activity in surface osteoblasts was elevated. PGE₂ produced similar immediate and sustained increases in G6PD activity, but no change in ALP activity.

[³H]thymidine incorporation was located autoradiographically to the nuclei of cells in the osteoblastic layer of the periosteum, and [³H]proline to the cytoplasm of periosteal osteoblasts and intercellular osteoid. In situ hybridisation showed that loading, PGE₂ and PGI₂ increased the expression of mRNA for type I collagen in these cells.

The implications of these results are discussed with regard to postmenopausal osteoporosis.