Regulation of bone mass by the gut microbiota is dependent on NOD1 and NOD2 signaling

• Germ-free (GF) mice have increased bone mass that is normalized by colonization with gut microbiota (GM) from conventionally raised (CONV-R) mice. To determine if innate immune signaling pathways mediated the effect of the GM, we studied the skeleton of GF and CONV-R mice with targeted inactivation of MYD88, NOD1 or NOD2. In contrast to WT and Myd88(-/-) mice, cortical bone thickness in mice lacking Nodi or Nod2 was not increased under GF conditions. The expression of Tnf alpha and the osteoclastogenic factor Rankl in bone was reduced in GF compared to CONV-R WT mice but not in Nodl(-/-) or Nod2(-/-) mice indicating that the effect of the GM to increase Tnfa and Rankl in bone and to reduce bone mass is dependent on both NOD1 and NOD2 signaling.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

Bone mass

Gut microbiota

Osteoclast

Immune system

Germ free mice

PERIODONTAL-DISEASE MODEL

TNF-ALPHA

MICE

PEPTIDOGLYCAN

RESORPTION

LIPOPOLYSACCHARIDE

OSTEOCLASTOGENESIS

MODULATION

BACTERIA

GROWTH

Publication and Content Type

ref (subject category)

art (subject category)