Onset and dynamics of osteosclerosis in mice induced by Reilly-Finkel-Biskis (RFB) murine leukemia virus - Increase in bone mass precedes lymphomagenesis

Newborn NMRI strain mice were infected with Reilly-Finkel-Biskis (RFB) muri ne leukemia virus (MuLV), a murine leukemia virus that has been shown to in duce lymphomas, osteosclerosis, and osteomas in susceptible strains of mice . Bone histomorphometry of the distal femoral metaphyses at S-month interva ls showed osteosclerosis 3 (100%), 6 (100%), and 9 (93%) months after infec tion. This was represented by significantly augmented cancellous bone mass and accompanied by distinct changes in bone architecture. High numbers of p rovirus copies were detected at 2-4 weeks in femora, humeri, and calvaria, and viral protein was highly expressed in trabecular and cortical bone cell s, particularly in osteocytes, Infected mice showed enhanced bone formation and smaller numbers of osteoclasts relative to sex- and matched controls, Osteoclastic differentiation was significantly reduced in cocultures of spl een or bone marrow cells with RFB MuLV-infected osteoclastogenic, osteoblas t-like cells. However, RFB MuLV did not impair the activity of mature osteo clasts, In infected mice lymphomas mere only observed at 6 (22%) and 3 mont hs (40%) of age. At 3 months, IgG gene and TCR-beta gene rearrangements wer e not detectable, and new proviruses showed a heterogeneous integration pat tern, indicating the absence of lymphoma in early osteosclerotic mice. In c ontrast, lymphomas, which developed in 8- to 9-month-old infected mice, sho wed IgG rearrangements indicating development of B-cell lymphomas, together with mono- or oligoclonal expansion of distinct patterns of proviral integ rations. These results indicate that RFB MuLV-induced osteosclerosis develo ps within 3 months after infection and precedes lymphomagenesis, It may the refore be considered an independent skeletal lesion in MuLV-infected mice.