Se. Asmus et al., Induction of cholinergic function in cultured sympathetic neurons by periosteal cells: Cellular mechanisms, DEVELOP BIO, 235(1), 2001, pp. 1-11
Periosteum, the connective tissue surrounding bone, alters the transmitter
properties of its sympathetic innervation during development in vivo and af
ter transplantation. Initial noradrenergic properties are downregulated and
the innervation acquires cholinergic and peptidergic properties. To elucid
ate the cellular mechanisms responsible, sympathetic neurons were cultured
with primary periosteal cells or osteoblast cell lines. Both primary cells
and an immature osteoblast cell line, MC3T3-E1, induced choline acetyltrans
ferase (ChAT) activity. In contrast, lines representing marrow stromal cell
s or mature osteoblasts did not increase ChAT. Growth of periosteal cells w
ith sympathetic neurons in transwell cultures that prevent direct contact b
etween the neurons and periosteal cells or addition of periosteal cell-cond
itioned medium to neuron cultures induced ChAT, indicating that periosteal
cells release a soluble cholinergic inducing factor. Antibodies against LIF
R beta, a receptor subunit shared by neuropoietic cytokines, prevented ChAT
induction in periosteal cell/neuron cocultures, suggesting that a member o
f this family is responsible. ChAT activity was increased in neurons grown
with periosteal cells or conditioned medium from mice lacking either leukem
ia inhibitory factor (LIE) or LIF and ciliary neurotrophic factor (CNTF). T
hese results provide evidence that periosteal cells influence sympathetic n
euron phenotype by releasing a soluble cholinergic factor that is neither L
IF nor CNTF but signals via LIFR beta.