Effect of mechanical stimulation on the production of soluble bone factors in cultured fetal mouse calvariae

Abstract

Mechanical stimulation by intermittent compressive force (ICF) stimulates bone formation and inhibits bone resorption in cultured fetal mouse bone. Fetal bone tissue can produce autocrine factors that stimulate bone cell replication and matrix formation, and paracrine factors that increase the formation of osteoclast precursor-like cells from bone marrow. In the present study, we have tested whether ICF affects the production of such local factors in fetal mouse calvariae. Calvariae were cultured for 4 days in the presence and absence of ICF (130 mbar, 0.3 Hz). Conditioned medium was collected daily and pooled. We found that conditioned medium from ICF-exposed cultures stimulated [3H]-TdR incorporation into DNA, and [3H]-proline incorporation into collagenase digestible protein but not into non-collagen protein in fresh calvarial cultures. Treatment with conditioned medium from ICF-exposed cultures had earlier effects on [3H]-TdR and [3H]-proline incorporation than direct treatment with ICF. Conditioned medium from ICF-exposed cultures decreased the number of osteoclast precursor-like cells in bone marrow cultures stained for tartrate-resistant acid phosphatase. We conclude that ICF stimulates the release (activity) of an autocrine growth-factor from bone. In addition, ICF can stimulate the release (activity) of a paracrine factor, inhibiting the growth and/or differentiation of osteoclast precursor-like cells. These data suggest that mechanical forces may modulate skeletal (re)modeling by affecting the production of local growth factors.

Proliferative and phenotypic responses of bone‐like cells to mechanical deformation

“…Hasegawa et al (19) demonstrated a 64% increase in proliferation of calvarial cells exposed to hyperphysiological strains of 40,000 p with a continuous single cycle of deformation. The current study, as well as others (6,9,20,21,25,29,30), documented proliferative responses (over a wide variety of plating and mechanical conditions) in which 8-64% of the cells were labeled. Therefore, in vitro descriptions of cellular response to mechanical strain often results in proliferative responses at high strain magnitudes.…”

Gabapentin Disrupts Binding of Perlecan to the α2δ1 Voltage Sensitive Calcium Channel Subunit and Impairs Skeletal Mechanosensation

“…Transmission of mechanical force from the bone matrix to the osteocyte cell membrane was initially thought to occur via direct sensing of whole-tissue strains on the osteocyte surface. However, strains applied to whole bone in vivo during normal locomotion are typically between 0.04–0.3% [ 2 , 3 ], an order of magnitude smaller than the strain necessary to elicit a biochemical response at the osteocyte plasma membrane (1–10%) [ 4 , 5 , 6 ]. Thus, a mechanism other than direct force transmission from the bone matrix must account for the ability of osteocytes to perceive mechanical input.…”

Gabapentin Disrupts Binding of Perlecan to the α2δ1Voltage Sensitive Calcium Channel Subunit and Impairs Skeletal Mechanosensation

“…3,4), an order of magnitude smaller than the strain necessary to elicit a biochemical response at the osteocyte plasma membrane (1-10%) (ref. [5][6][7]. Thus, a mechanism other than direct force transmission from the bone matrix must account for the ability of osteocytes to perceive mechanical input.…”