Biglycan-deficient mice have delayed osteogenesis after marrow ablation.
Biglycan (bgn) is a small proteoglycan in skeletal tissue that binds and regulates collagen and TGF-beta activities. Mice deficient in bgn (bgn-KO) develop age-dependent osteopenia and have multiple metabolic defects in their bone marrow stromal cells including increased apoptosis, reduced numbers of colony-forming units-fibroblastic (CFU-F) and decreased collagen production. In the present study we tested the hypothesis that bone formation capability in response to a physiological stress is compromised in bgn deficiency. We tested this theory using an in vivo bone marrow ablation assay. Ablation was performed on 6-week-old wild type (wt) and bgn-KO mice and bones were analyzed at days 7, 10, and 17 postsurgery. X-ray analysis showed that bone marrow ablation in femora induced vigorous new bone formation within 10 days in both genotypes but appeared greater in the wt compared to the bgn-KO. In order to quantitate the changes in bone formation in the ablated animals, bone densities of the proximal, midshaft, and distal femora were assessed using peripheral quantitative computed tomography (pQCT). The ratio of cancellous bone density at the midshaft (ablated limb/control limb) was significantly higher in wt compared to bgn-KO at day 10 postsurgery. Wt and bgn-KO femora had similar total and cancellous bone densities at days 7 and 17 postsurgery at all three locations indicating that the ablation effects were temporal and limited to the cancellous bone of the mid-shaft region. These data indicate that the absence of bgn directly impeded bone formation. Our results support the concept that bgn is important in controlling osteogenesis following marrow ablation.
Chen
X-D
XD
Craniofacial & Skeletal Disease Branch, NIDCR, Bethesda, MD, USA.
Allen
M R
MR
Bloomfield
S
S
Xu
T
T
Young
M
M
D000818:Animals; D058578:Biglycan; D015519:Bone Density; D001853:Bone Marrow / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D016326:Extracellular Matrix Proteins; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010012:Osteogenesis / Q000502:physiology*; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics; D017154:Stromal Cells; D014057:Tomography, X-Ray Computed
C546885:Bgn protein, mouse; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans