Osteoclast size heterogeneity in rat long bones is associated with differences in adhesive ligand specificity.
Prothrombin (PT) is an RGD-containing bone-residing precursor to the serine protease thrombin (TH), which acts as an agonist for a variety of cellular responses in osteoblasts and osteoclasts. We show here that PT, TH, osteopontin (OPN) and fibronectin (FN) promoted adhesion of isolated neonatal rat long bone osteoclasts. However, the cells that adhered to PT and TH were smaller in size, rounded and contained 3-4 nuclei, in comparison to the cells adhering to OPN and FN, which were larger with extended cytoplasmic processes and 6-7 nuclei. Attachment of the larger osteoclasts to OPN and FN was inhibited by antibodies towards beta 3 and beta 1 integrin subunits, respectively. Whereas an RGD-containing peptide inhibited adhesion of the smaller osteoclasts to PT and TH, this was not seen with the beta 3 or beta 1 antibodies. In contrast, the beta 1 antibody augmented osteoclast adhesion to PT and TH in an RGD-dependent manner. Small osteoclasts were less efficient in resorbing mineralized bovine bone slices, as well as expressed lower mRNA levels of MMP-9 and the cathepsins K and L compared to large osteoclasts. The small osteoclast adhering to PT and TH may represent either an immature, less functional precursor to the large osteoclast or alternatively constitute a distinct osteoclast population with a specific role in bone.
Hu
Yingwei
Y
Center for Oral Biology, Department of Odontology, Karolinska Institutet, SE-141 04 Huddinge, Sweden.
Ek-Rylander
Barbro
B
Karlström
Erik
E
Wendel
Mikael
M
Andersson
Göran
G
D000818:Animals; D000831:Animals, Newborn; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D039641:Integrin beta Chains / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism / Q000494:pharmacology; D011516:Prothrombin / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039641:Integrin beta Chains; D008024:Ligands; C506896:Spp1 protein, mouse; D053495:Osteopontin; D011516:Prothrombin; D002403:Cathepsins; D013917:Thrombin; D020780:Matrix Metalloproteinase 9