Osteoporosis limits neurological recovery after spinal cord injury through PDGF-BB-MMP14 signaling

Osteoporosis may limit recovery from spinal cord injuries, and teriparatide has shown potential in improving bone structure and recovery outcomes.

Summary and findings

This study examined the association between bone status and neurological recovery in 324 patients with traumatic spinal cord injury (SCI) and tested mechanisms in mice with osteoporosis. Teriparatide improved trabecular bone structure and promoted locomotor recovery. The study highlights osteoporosis as a modifier of SCI recovery.

Abstract

<title>Abstract</title> <p>Osteoporosis is usually regarded as a downstream skeletal complication of spinal cord injury (SCI), but whether it reciprocally limits spinal cord repair is unclear. We examined the association between bone status and 1-year neurological recovery in a retrospective cohort of 324 patients with traumatic SCI and tested potential mechanisms in mice with ovariectomy-induced osteoporosis followed by SCI. In-house and public transcriptomic datasets, single-nucleus RNA sequencing, pharmacological interventions and a pericyte-endothelial co-culture model were integrated to investigate platelet-derived growth factor-BB (PDGF-BB)-matrix metalloproteinase 14 (MMP14) signaling. Osteopenia and osteoporosis were independently associated with markedly lower odds of American Spinal Injury Association Impairment Scale grade improvement. Osteoporotic SCI mice showed poorer locomotor recovery, greater neuronal loss and glial scarring, and more severe blood-spinal cord barrier disruption. Integrated analyses prioritized MMP14 and localized its post-injury expression mainly to vascular cells, including PDGFRB-positive pericytes. The MMP14-targeting compound NSC 405020 improved barrier integrity and neurological recovery, whereas sustained recombinant PDGF-BB exposure increased pericyte-associated MMP14 and partially reproduced the osteoporotic SCI phenotype. Teriparatide improved trabecular bone structure, reduced tibial PDGF-B and spinal pericyte-associated MMP14 signals, preserved the blood-spinal cord barrier and promoted locomotor recovery. These findings identify osteoporosis as a systemic modifier of SCI recovery and support PDGF-BB-MMP14 signaling as a targetable link between skeletal remodeling and neurovascular repair.</p>

Elsewhere in the Teriparatide (PTH 1-34) corpus