Early Responses to Dynamic Strain Change and Prostaglandins in Bone-Derived Cells in Culture

Abstract

Mechanical loading of bone explants stimulates prostaglandin E 2 (PGE 2 ) and prostacyclin (PGI 2 ) release and increases glucose 6-phosphate dehydrogenase (G6PD) activity. This response is blocked by indomethacin and imitated by exogenous PGs. In the experiments reported here, primary cultures of rat long bone-derived osteoblast-like cells were exposed to a dynamic strain and exogenous PGs in the culture dish. Strain (3400 , 600 cycles, 1 Hz) caused an immediate release of PGI 2 into the culture medium but had no effect on PGE 2 . Strain also caused an increase in G6PD activity per cell and an increase in the smallest transcript of insulin-like growth factor II (IGF-II) (IGF-II T3) but had no effect on the expression of transforming growth factor-␤1 (TGF-␤1). Indomethacin inhibited strain-induced release of PGI 2 and suppressed strain-induced stimulation of IGF-II T3 transcript. PGI 2 (1 M) increased G6PD activity and mRNA levels of all three transcripts of IGF-II but had no effect on the mRNA levels of IGF-I or TGF-␤1. PGE 2 (1 M) stimulated G6PD activity and caused a marked increase in IGF-I and the largest transcript of IGF-II (IGF-II T1) but had no effect on the IGF-II transcripts T2 and T3 or on TGF-␤1 mRNA levels. These findings show similarities in response between osteoblast-like cells strained in monolayer culture and bone cells in loaded bone explants in situ. They provide support for a role for IGF-II and PGI 2 in the early strain-related response of osteoblasts in loading-related bone modeling/remodeling. (J Bone Miner Res 1997;12:769-777)

Wnt/β-Catenin Signaling Is a Component of Osteoblastic Bone Cell Early Responses to Load-bearing and Requires Estrogen Receptor α

“…ER␣-null mutant mice (ER␣ Ϫ/Ϫ ) (31) were a gift from Professor Pierre Chambon. Cell Culture-Primary osteoblast-like cells were prepared from the long bones of 17-week-old female ER␣ Ϫ/Ϫ mice and their WT littermates as previously described (32).…”

A Specific Mechanomodulatory Role for p38 MAPK in Embryonic Joint Articular Surface Cell MEK-ERK Pathway Regulation

“…The mechanical strain stimulus comprised uniaxial dynamic (1 Hz) mechanical strain with a peak magnitude of 3800 ⑀. This was applied for 10 min using a specifically designed loading jig by four-point bending of plastic strips (Nunc) onto which the cells had been seeded as previously described (25,(27)(28)(29). This essentially imparts tensile strain in a controlled manner by bending of the cell culture-treated plastic strips onto which cells have been previously seeded.…”

Role of Prostaglandin I2in the Gene Expression Induced by Mechanical Stress in Spinal Ligament Cells Derived from Patients with Ossification of the Posterior Longitudinal Ligament

“…It has been reported that mechanical stress plays an important role in the progression of OPLL (Kitajima et al, 2001). Furthermore, mechanical stress produces PGI 2 in osteoblasts (Rawlinson et al, 1993;Zaman et al, 1997). To investigate the relationship between PGI 2 signaling and mechanical stress, we performed RT-PCR with primers for PGI 2 synthase.…”