NF-κB–inducing kinase controls lymphocyte and osteoclast activities in inflammatory arthritis
J. Clin. Invest. Kunihiko Aya, et al. 115:1848 doi:10.1172/JCI23763 [Go to this article.]

Figure 2
Histological evaluation of STA. Hind paws from control mice (A, D, and G) and from Nik+/+ (B, E, and H) and Nik–/– (C, F, and I) mice with STA at day 14 were sectioned and stained with H&E (A–F) or TRAP (G–I). In control sections (A and D), bones were closely apposed, with smooth surfaces and no inflammatory infiltrate. The TRAP stain (G) shows scattered OCs (stained red) at bone/marrow interfaces (arrowheads) but none on bone surfaces. In contrast, Nik+/+ paws from serum-injected mice (B and E) had an extensive inflammatory infiltrate in the joint spaces. In the TRAP stain (H), OCs were prominent in marrow (arrowheads) and on bone surfaces (arrows), particularly where the inflammatory pannus was adjacent. In these areas, the bone surface was irregular, which indicates bone erosion. Nik–/– mice with arthritis (C and F) show an inflammatory infiltrate similar to that of Nik+/+ mice. However, bone contours remain smooth. The TRAP stain (I) shows OCs within the marrow (arrowhead) but few on bone surfaces, even where adjacent to pannus (arrow). Scale bar: 500 μm for A–C; 200 μm for D–F; and 100 μm for G–I. (J) Histological sections were scored for inflammation (left) based on H&E stains and for bone erosion (right) based on TRAP stains according to an arbitrary scale of 0–3. (K) TRAP-stained sections were evaluated by histomorphometry in the regions shown in H–I. The mean number of OCs per mm (± SD) present on the bone surface (left) and at the marrow interface (right) is shown. (*P < 0.01; **P < 0.00005, Nik–/– compared with Nik+/+; n = 7–8 per group). (L) Serum levels of TRAP5b, a form of the enzyme specific for active OCs, were determined 1 day prior to first serum injection (pre) and at day 14 (STA). *P < 0.01 compared with pre-injection Nik+/+ by paired Student’s t test; n = 4)