Morphological and functional features of clasts in low phosphate, vitamin D-deficiency rickets.
Focusing on resorption processes, we have extended our previous studies on chondroclasts and osteoclasts in normally developing tissues, using a model of nutritionally induced vitamin D-deficiency rickets. To analyze the resorption process, we investigated the matrix-resorbing cells in this modified and poorly mineralized tissue regarding morphological features and expression of tartrate-resistant acid phosphatase (TRAP) at the subcellular level. Our goal was to test the hypotheses that initiation of resorption is impaired with unmineralized matrix, and that such alterations involve changes in the subcellullar distribution of TRAP, implicating a role for this enzyme in the resorption process. Our results reveal distinctly different morphological appearances of clast-like cells in rickets compared with normal osteoclasts and chondroclasts. Ordinary resorption structures of osteoclasts and chondroclasts at the cell-matrix border, i.e., ruffled borders and clear zones, are profoundly altered in favor of a less well-defined intermediate zone. TRAP distribution at the subcellullar level is also clearly different from that in osteoclasts and chondroclasts from normal rodents, with impaired secretion; consequently, the enzyme is unable to function in the matrix outside the ruffled border. Our ultrastructural observations demonstrate that in rickets, the clasts are incapable of degrading the poorly mineralized cartilage and bone efficiently. Rachitic clasts seem to be recruited to the matrix surface and interaction between cell and matrix is also initiated, but definitive resorption structures at the cell-matrix border are not normally developed. Whether resorption is inhibited by the mere lack of mineral or mineral-associated proteins, or by other mechanisms remains to be settled.
Nordahl
J
J
Department of Immunology, Microbiology, Pathology and Infectious Diseases, Division of Pathology, Karolinska Institutet, Huddinge Hospital, F 46 S - 141 86 Huddinge, Sweden.
Hollberg
K
K
Mengarelli-Widholm
S
S
Andersson
G
G
Reinholt
F P
FP
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001862:Bone Resorption / Q000378:metabolism*; D007015:Hypophosphatemia, Familial / Q000378:metabolism* / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010010:Osteoclasts / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D007527:Isoenzymes; D010710:Phosphates; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase