Abstract
Identifying mechanisms by which cells of the osteoblastic lineage communicate in vivo is complicated by the mineralised matrix that encases osteocytes, and thus, vital mechanoadaptive processes used to achieve load‐bearing integrity remain unresolved. We have used the coculture of immunomagnetically purified osteocytes and primary osteoblasts from both embryonic chick long bone and calvariae to examine these mechanisms. We exploited the fact that purified osteocytes are postmitotic to examine both their effect on proliferation of primary osteoblasts and the role of gap junctions in such communication. We found that chick long bone osteocytes significantly increased basal proliferation of primary osteoblasts derived from an identical source (tibiotarsi). Using a gap junction inhibitor, 18β‐glycyrrhetinic acid, we also demonstrated that this osteocyte‐related increase in osteoblast proliferation was not reliant on functional gap junctions. In contrast, osteocytes purified from calvarial bone failed to modify basal proliferation of primary osteoblast, but long bone osteocytes preserved their proproliferative action upon calvarial‐derived primary osteoblasts.We also showed that coincubated purified osteocytes exerted a marked inhibitory action on mechanical strain–related increases in proliferation of primary osteoblasts and that this action was abrogated in the presence of a gap junction inhibitor. These data reveal regulatory differences between purified osteocytes derived from functionally distinct bones and provide evidence for 2 mechanisms by which purified osteocytes communicate with primary osteoblasts to coordinate their activity.
Highlights
There is much evidence supporting the view that osteocytes act as strain sensors in bones
A potential route by which osteocytes could influence the behaviour of overlying osteoblasts in response to external mechanical stimuli is via the passage of small molecules through the osteoblast: osteocyte network of gap junctions or via molecules secreted into the intralacunar fluid
To determine whether gap junction communication is required for LOC‐induced LOB proliferation and whether it contributes to bone cell responses to mechanical strain, we examined the effect of the gap junction blocker, β‐glycyrrhetinic acid (β‐GA), in homogenic long bone cocultures (LOC + LOB) both with and without mechanical strain stimulation
Summary
There is much evidence supporting the view that osteocytes act as strain sensors in bones. A potential route by which osteocytes could influence the behaviour of overlying osteoblasts in response to external mechanical stimuli is via the passage of small molecules through the osteoblast: osteocyte network of gap junctions or via molecules secreted into the intralacunar fluid This fluid bathes osteocytes and the bone‐facing processes of osteoblasts and lining cells, and its movement through canaliculae results from the pressure differentials induced by dynamic loads. We have examined these osteocyte‐osteoblast interactions and the role of gap junction–mediated communication further This has been achieved by investigating, for the first time, the influence exerted by purified embryonic chick bone osteocytes upon the proliferation of primary osteoblasts in direct contact coculture. They demonstrate that purified osteocytes can regulate behaviour of primary osteoblasts and that the functional outcome of this communication differs markedly when the proliferative response of osteoblasts to mechanical strain is examined
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