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Updated: Oct 13, 2025
Longitudinal Evaluation of Mouse Hind Limb Bone Loss After Spinal Cord Injury using Novel, in vivo, Methodology
Published on: December 7, 2011
Inhibition of TGF-β Signaling Attenuates Disuse-induced Trabecular Bone Loss After Spinal Cord Injury in Male Mice
Karim Sahbani1,2, Christopher P Cardozo1,2,3,4,5, William A Bauman1,2,3,4,5
1National Center for the Medical Consequences of Spinal Cord Injury, James J Peters Veterans Affairs Medical Center, Bronx, NY 10468, USA.
Abstract:
Bone loss is one of the most common complications of immobilization after spinal cord injury (SCI). Whether transforming growth factor (TGF)-β signaling plays a role in SCI-induced disuse bone loss has not been determined. Thus, 16-week-old male mice underwent sham or spinal cord contusion injury to cause complete hindlimb paralysis. Five days later, 10 mg/kg/day control (IgG) or anti-TGF-β1,2,3 neutralizing antibody (1D11) was administered twice weekly for 4 weeks. Femurs were examined by micro-computed tomography (micro-CT) scanning and histology. Bone marrow (BM) supernatants were analyzed by enzyme-linked immunosorbent assay for levels of procollagen type 1 intact N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase (TRAcP-5b), receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and prostaglandin E2 (PGE2). Distal femoral micro-CT analysis showed that SCI-1D11 mice had significantly (P < .05) attenuated loss of trabecular fractional bone volume (123% SCI-1D11 vs 69% SCI-IgG), thickness (98% vs 81%), and connectivity (112% vs 69%) and improved the structure model index (2.1 vs 2.7). Histomorphometry analysis revealed that osteoclast numbers were lower in the SCI-IgG mice than in sham-IgG control. Biochemically, SCI-IgG mice had higher levels of P1NP and PGE2 but similar TRAcP-5b and RANKL/OPG ratio to the sham-IgG group. The SCI-1D11 group exhibited higher levels of P1NP but similar TRAcP-5b, RANKL/OPG ratio, and PGE2 to the sham-1D11 group. Furthermore, 1D11 treatment prevented SCI-induced hyperphosphorylation of tau protein in osteocytes, an event that destabilizes the cytoskeleton. Together, inhibition of TGF-β signaling after SCI protects trabecular bone integrity, likely by balancing bone remodeling, inhibiting PGE2 elevation, and preserving the osteocyte cytoskeleton.
Insights
Inhibition of transforming growth factor (TGF)-β signaling protects bone integrity after spinal cord injury (SCI). This study shows TGF-β blockade preserves trabecular bone by balancing remodeling and protecting osteocyte cytoskeleton.
Area of Science:
- Biomedical Engineering
- Orthopedics
- Neuroscience
Background:
- Spinal cord injury (SCI) frequently leads to bone loss due to disuse.
- The role of transforming growth factor (TGF)-β signaling in SCI-induced bone loss remains unclear.
Purpose of the Study:
- To investigate the effect of inhibiting TGF-β signaling on bone loss following SCI in mice.
- To determine if TGF-β blockade can preserve bone structure and cellular integrity after SCI.
Main Methods:
- Mice with SCI underwent treatment with either a control antibody (IgG) or an anti-TGF-β neutralizing antibody (1D11).
- Bone structure was analyzed using micro-computed tomography (micro-CT) and histomorphometry.
- Bone marrow supernatants were analyzed for biochemical markers of bone turnover and inflammation.
Main Results:
- Anti-TGF-β (1D11) treatment significantly attenuated the loss of trabecular bone volume, thickness, and connectivity in SCI mice compared to controls.
- Histomorphometry showed reduced osteoclast numbers in SCI mice treated with IgG.
- 1D11 treatment prevented SCI-induced hyperphosphorylation of tau protein in osteocytes.
Conclusions:
- Inhibition of TGF-β signaling effectively protects trabecular bone integrity after SCI.
- TGF-β blockade likely preserves bone by balancing remodeling, reducing prostaglandin E2 (PGE2) levels, and maintaining osteocyte cytoskeletal stability.
