Laminins 2 (alpha2beta1gamma1, Lm-211) and 8 (alpha4beta1gamma1, Lm-411) are synthesized and secreted by tooth pulp fibroblasts and differentially promote neurite outgrowth from trigeminal ganglion sensory neurons.
The tooth pulp innervation originates from the trigeminal ganglion (TG) and represents an illustrative example of tissue targeting by sensory nerves. Pulpal fibroblasts strongly promote neurite outgrowth from TG neurons in vitro. In the present study, we have investigated the possible participation of laminins (LNs), potent neuritogenic extracellular matrix components. Immunohistochemistry of human tooth pulp demonstrated expression of LN alpha1, alpha2, alpha4, alpha5, beta1 and gamma1, and laminin-binding integrin alpha3, alpha6, beta1 and beta4 chains in nerves. Though faintly stained for laminins in situ, pulpal fibroblasts reacted, once cultured and permeabilized, with antibodies to LN alpha2, alpha4, beta1 and gamma1 chains by flow cytometry. The cells also expressed the corresponding mRNAs and were able to assemble and secrete LN-2 (alpha2beta1gamma1, Lm-211) and LN-8 (alpha4beta1gamma1, Lm-411). LN-8 displayed a chondroitin sulphate (CS) modification in its alpha4 chain. In functional assays, mouse LN-1 (alpha1beta1gamma1, Lm-111) and recombinant human (rh) LN-8, but not native or rhLN-2, strongly promoted neurite outgrowth from TG neurons, mimicking the effect of cultured pulp fibroblast. Altogether, the results indicate that LN-2 and LN-8 are synthesized by tooth pulp fibroblasts and differentially promote neurite outgrowth from TG neurons. LN-8 may contribute to sensory innervation of teeth and other tissues during development and/or regeneration.
Fried
Kaj
K
Center for Oral Biology, Department of Odontology, Karolinska Institutet at Huddinge, Stockholm, Sweden.
Sime
Wondossen
W
Lillesaar
Christina
C
Virtanen
Ismo
I
Tryggvasson
Karl
K
Patarroyo
Manuel
M
D000293:Adolescent; D000328:Adult; D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000166:cytology
D016023:Integrins; C501369:LAMA4 protein, human; C478221:LAMB1 protein, human; C501370:Lama4 protein, mouse; C513277:Lamb1 protein, mouse; D007797:Laminin; D020033:Protein Isoforms; D021122:Protein Subunits; C110308:laminin 8; C102645:laminin alpha 2; C089141:laminin gamma 1; D002809:Chondroitin Sulfates