Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen.
Mice carrying a targeted mutation (r) in Col1a1, encoding a collagenase-resistant form of type I collagen, have altered skeletal remodeling. In hematoxylin and eosin-stained paraffin sections, we detect empty lacunae in osteocytes in calvariae from Col1a1(r/r) mice at age 2 weeks, increasing through age 10-12 months. Empty lacunae appear to result from osteocyte apoptosis, since staining of osteocytes/periosteal osteoblasts with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling is increased in Col1a1(r/r) relative to wild-type bones. Osteocyte perilacunar matrices stained with Ab that recognizes collagenase collagen alpha1(I) chain cleavage ends in wild-type but not Col1a1(r/r) calvariae. Increased calvarial periosteal and tibial/femoral endosteal bone deposition was found in Col1a1(r/r) mice from ages 3-12 months. Calcein labeling of calvarial surfaces was increased in Col1a1(r/r) relative to wild-type mice. Daily injections of synthetic parathyroid hormone for 30 days increased calcein-surface labeling in wild-type but caused no further increase in the already high calcein staining of Col1a1(r/r) bones. Thus, failure of collagenase cleavage of type I collagen in Col1a1(r/r) mice is associated with osteocyte/osteoblast death but increases bone deposition in a manner that mimics the parathyroid hormone-induced bone surface activation seen in wild-type mice.
Zhao
W
W
Department of Medicine, Harvard Medical School, Medical Services (Arthritis Unit), Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Byrne
M H
MH
Wang
Y
Y
Krane
S M
SM
D000818:Animals; D017209:Apoptosis; D016723:Bone Remodeling / Q000235:genetics*; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D005269:Femur / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010006:Osteoblasts / Q000473:pathology*; D010011:Osteocytes / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D013977:Tibia / Q000473:pathology
D010281:Parathyroid Hormone; D003094:Collagen; D017364:Collagenases