Effects of 1,25 dihydroxyvitamin D on osteoclast number and cytochemistry in normal and osteopetrotic (os) rabbits.
Osteoclast-mediated bone resorption is increased in response to 1,25 dihydroxyvitamin D (1,25[OH]2D or calcitriol). Osteopetrosis is a metabolic bone disease characterized by defective, osteoclast-mediated bone resorption, which co-exists with elevated serum 1,25-(OH)2D levels in some osteopetrotic children and animals. We examined the effects of high doses of calcitriol on osteoclast number and cytochemistry in both normal and osteopetrotic (os) rabbits. Calcitriol was continuously infused at doses of 0.5, 2.5, or 25 micrograms/kg/day via subcutaneously implanted osmotic minipumps for a period of 7 days. Following treatment, the proximal tibial metaphyses were processed for histomorphometric and cytochemical analyses. Sections were stained for tartrate-resistant acid phosphatase (TrAP) or acid ATPase (TraATPase). Osteoclasts were significantly reduced in untreated os rabbits compared with age-matched normal littermates between birth and 3 weeks of age (41-46% of normal). Whereas most normal osteoclasts (85%) stained heavily for TrAP or TraATPase, less than half of os osteoclasts were heavily stained for these acid hydrolases. Infusions of 1,25(OH)2D resulted in elevations of osteoclast numbers in both normal and os rabbits, but the number of osteoclasts remained significantly lower in mutants than in normal littermates at any given dose. Calcitriol infusions also resulted in a significant increase in the percentage of os osteoclasts staining heavily for TrAP and TraATPase. These results suggest that in response to 1,25(OH)2D normal osteoclasts increase their production of acid hydrolases before increasing cell numbers and that, in spite of high levels of endogenous calcitriol, os rabbits can respond to exogenous 1,25(OH)2D as evidenced by increased osteoclast number and cytochemical staining, even though these osteoclasts fail to resorb the excess skeletal matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
Grise
M A
MA
Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655.
Marks
S C
SC
MacKay
C A
CA
Popoff
S N
SN
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D010022:Osteopetrosis / Q000473:pathology*; D011817:Rabbits
D000251:Adenosine Triphosphatases; D002117:Calcitriol