engleski

Genetic variability of new bone induction in mice

We studied differences in ectopic osteoinduction in 8 mouse inbred strains and 1 outbred strain. Antigen-extracted autolyzed rat bone gelatin was implanted under hind limb muscle fascia of 12 week-old males and new bone formation was morphologically assessed on serial sections. Four weeks after implantation, half or less than a half of the implants from CBA/J, A/J, BALB/cJ, and C3Hf/Bu inbred mice showed induction of cartilage only. New cartilage was observed in all and bone and bone marrow in 80% of implants from AKR/J, C57BL/6J, DBA/2J, and RFM/Rij inbred mice. Volume of the newly formed tissue ranged from 1.3% of the old matrix in A/J strain to 74.6% in DBA/2J strain. Outbred CD1 mice showed only weak cartilage induction. Expression of bone-related proteins was assessed by RT-PCR in 2 "good" responder (C57BL/6J and DBA/2J) and 3 "poor" responder (BALB/cJ, C3Hf/Bu, and A/J) strains. mRNAs for bone morphogenetic protein (BMP)-2 and BMP-4 had a similar temporal pattern of expression and were abundant in implants from C57BL/6 and C3Hf/Bu mice. BMP-7 mRNA was expressed in implants from all strains at all time points. Alkaline phosphatase mRNA was downregulated at 4 weeks after implantation in all strains but the enzyme activity correlated with the volume of the newly formed tissue. At 2 post-implantation weeks, osteocalcin mRNA was expressed in all implants with new cartilage and at 4 weeks it was detected in implants from DBA/2J, C57BL/6J, and C3Hf/Bu mice. IFN-? transcripts were detected in all strains at 2 weeks but were not expressed in "good" responder strains at 4 weeks after implantation. Immunological reaction to rat matrix is not the only explanation for the differences among the strains because the gelatin preparation was of low antigenicity and there was no segregation of H-2 haplotypes between "poor" and "good" responder strains. Our results show that adult mice of inbred strains differ not only in the morphology of their bones but also the ability to form new bone by endochondral ossification. Ectopic osteoinduction may be a useful model to investigate genetic determinants of a complex interplay of cytokines and growth factors during osteogenesis.

bone; bone morphogenetic proteins; cytokines; genetics; inbred mouse strains; osteoinduction

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