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Graduate School of Biomedical Sciences

The Volkhard Lindner Lab

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Functions

The Lindner laboratory discovered CTHRC1 in a screen for novel sequences specifically induced in injured arteries where it is highly induced in activated fibroblasts of the adventitia. Our subsequent studies revealed that CTHRC1 functions as a hormone with constitutive expression observed in the hypothalamus (Fig. 1A) and bone (Fig. 1B). In addition, we have occasionally observed CTHRC1 expression in the pituitary gland (Fig. 1C).

Lindner Fig 1

Figure 1. (A) CTHRC1 is expressed in the paraventricular nucleus of the hypothalamus and (B) by osteocytes and osteoblasts in bone. (C) Cells in the anterior pituitary gland were found to express CTHRC1 in some cases.

CTHRC1 is a novel metabolic regulator.

Lindner Fig 2

Figure 2. Cthrc1 null mice show metabolic abnormalities with development of fatty livers (A, B) and increased body fat (in pink C, D), while muscle mass is reduced in the absence of any muscle pathology. Of note, there is no CTHRC1 expression in liver or muscle despite development of pathology in these organs.

CTHRC1 has potent anti-inflammatory effects inhibiting NF-κB activation

Lindner Fig 3

Figure 3. The response of wildtype (A) and Cthrc1 null mice (B) to collagen antibody induced arthritis was evaluated. Cthrc1 null mice revealed severe inflammation with extensive bone and cartilage erosion. (C) Mechanistically we found that CTHRC1 potently inhibits NF-κB activation in RAW264.7 cells in response to RANKL stimulation.

CTHRC1 blood levels are detectable only in a minority of healthy human subjects

Lindner Fig 4

Figure 4. We developed sensitive monoclonal antibodies for detection of CTHRC1 by ELISA and observed that levels are below detection in approximately 70% of healthy human subjects. In some subjects levels exceeded 75ng/ml.