Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen
Weiguang Zhao, … , Yingmin Wang, Stephen M. Krane
Weiguang Zhao, … , Yingmin Wang, Stephen M. Krane
Published October 15, 2000
Citation Information: J Clin Invest. 2000;106(8):941-949. https://doi.org/10.1172/JCI10158.
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Article

Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen

Abstract

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 Col1a1r/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 Col1a1r/r relative to wild-type bones. Osteocyte perilacunar matrices stained with Ab that recognizes collagenase collagen α1(I) chain cleavage ends in wild-type but not Col1a1r/r calvariae. Increased calvarial periosteal and tibial/femoral endosteal bone deposition was found in Col1a1r/r mice from ages 3–12 months. Calcein labeling of calvarial surfaces was increased in Col1a1r/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 Col1a1r/r bones. Thus, failure of collagenase cleavage of type I collagen in Col1a1r/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.

Authors

Weiguang Zhao, Michael H. Byrne, Yingmin Wang, Stephen M. Krane

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Calcein labeling of bone surfaces from 3-month-old wild-type and Col1a1r...
Calcein labeling of bone surfaces from 3-month-old wild-type and Col1a1r/r mice. (a) Frozen sections of calvariae, examined by fluorescence microscopy, from mice given vehicle alone or PTH daily and injected with single doses of calcein at 1 and 11 days before sacrifice (see Methods). The outer periosteal surface in the sample from the vehicle-treated wild-type mouse is indicated by the solid open bar and the inner surface by the dashed open bar. In this section of calvariae from the untreated wild-type mice, the fluorescent calcein label was limited to inside the bone marrow cavity; only scattered label was seen occasionally at the outer periosteal surface. In the Col1a1r/r mice, marked and extensive labeling was evident at both periosteal surfaces. Note that the increased calvarial thickness in the 3-month-old Col1a1r/r mice. In the PTH-treated wild-type mice, there was marked calcein labeling at both surfaces. The calcein labeling, already extensive in the untreated Col1a1r/r mice, was not further increased by PTH. (b) Quantification of calcein labeling of active calvarial surfaces. (c) Quantification of bone apposition rate on active calvarial surfaces.