Fig 2: CTR-deficiency results in increased histopathological signs of arthritis(A) Histopathological inflammation, cartilage degradation, and bone erosion scores of ankle joints on day 10 and 48.(B) Clinical presentation of ankle joints on day 8.(C) Representative histopathological H&E-stained sections of ankle joints showing synovial hyperplasia, immune cell infiltration, and edema (white boxes), (D) toluidine-blue-stained sections showing cartilage degradation, indicated by loss of stain intensity (proteoglycan loss) and focal cartilage defects (black arrows) and (E) TRAP-stained sections with bone resorption zones, marked by stained osteoclast areas (white arrows) on day 10. Scale bars 500 µm. Given values are median ± minimum and maximum.

Fig 3: The CTR is essential to contain excessive expression of inflammation markersqRT-PCR expression analyses of inflammation and immunomodulation genes of ankle joints on day 10 and 48. Given values are median ± minimum and maximum as relative fold changes of WT CAIA and Calcr−/− CAIA groups with respect to CTRL groups that were set to 1.

Fig 4: Deficiency in CTR (Calcr-/-) does not significantly affect bone regeneration. Representative µCT images (left column = sagittal overview; right column = sagittal detailed view) of the callus region in WT and Calcr-/- mice at day 14 and day 21 following osteotomy. Three representative images are shown for each group and time point. In the sagittal view, newly mineralized callus is indicated in red, whereas the original bone is displayed in grey.

Fig 5: Interruption of CT/CTR-signaling does not significantly alter callus bridging. (A) Exemplary callus images (Movat Pentachrome staining) at day 21 following osteotomy, indicating the four different scores used for the following semiquantitative measurement of callus bridging. a = complete bridging (all four cortices bridged by callus; image derived from Calcr-/-), b = partial bridging (two to three cortices bridged by callus; image derived from Calcr-/-), c = incomplete bridging (callus present, but no bridging visible; image derived from WT), and d = nonunion (rounded cortices, minimal presence of callus; image derived from Calcr-/-). Scale bars = 500 µm. (B) Semi-quantitative evaluation of callus bridging in WT and CTR-deficient mice at day 21 following osteotomy in the callus sections of WT and Calcr-/- mice the indicated time points by two blinded investigators. n = 4–6 mice per group. Box plots represent median with minimum and maximum whiskers.