Oral citrate supplementation mitigates age-associated pathological intervertebral disc calcification in LG/J mice.

Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate the efficacy of long-term oral KCitrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. KCitrate successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion.

Corrigendum: The cGAS-STING pathway affects vertebral bone but does not promote intervertebral disc cell senescence or degeneration.

[This corrects the article DOI: 10.3389/fimmu.2022.

The cGAS-STING Pathway Affects Vertebral Bone but Does Not Promote Intervertebral Disc Cell Senescence or Degeneration.

The DNA-sensing cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) and mediates type-I interferon inflammatory responses to foreign viral and bacterial DNA as well as self-DNA. Studies of the intervertebral disc in humans and mice demonstrate associations between aging, increased cell senescence, and disc degeneration. Herein we assessed the role of STING in SASP promotion in STING gain- (N153S) and loss-of-function mouse models.

Sox9 deletion causes severe intervertebral disc degeneration characterized by apoptosis, matrix remodeling, and compartment-specific transcriptomic changes.

SOX9 plays an important role in chondrocyte differentiation and, in the developing axial skeleton, maintains the notochord and the demarcation of intervertebral disc compartments. Diminished expression is linked to campomelic dysplasia, resulting in severe scoliosis and progressive disc degeneration. However, the specific functions of SOX9 in the adult spinal column and disc are largely unknown.

Differential Effect of Long-Term Systemic Exposure of TNFα on Health of the Annulus Fibrosus and Nucleus Pulposus of the Intervertebral Disc.

The inflammatory cytokine tumor necrosis factor alpha (TNFα) is considered to play a key role in the pathogenesis of intervertebral disc disease. To evaluate the importance of this cytokine we examined the inflammatory environment and spinal phenotype of 9-month-old human TNFα overexpressing transgenic (hTNFα-TG) mice. The mice evidenced increased circulating levels of interleukin-1β (IL-1β), IL-2, keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO), and monocyte chemoattractant protein-1 (MCP-1) along with thinning of the cortical and trabecular vertebral bone.

TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression.

The tonicity-responsive enhancer binding protein (TonEBP) plays an important role in intervertebral disc and axial skeleton embryogenesis. However, the contribution of this osmoregulatory transcription factor in postnatal intervertebral disc homeostasis is not known in vivo. Here, we show for the first time that TonEBP-deficient mice have pronounced age-related degeneration of the intervertebral disc with annular and endplate herniations.