Proteoglycan Dysfunction as a Key Hallmark of Intervertebral Disc Degeneration: Commentary on “Proteoglycan Dysfunction: A Common Link Between Intervertebral Disc Degeneration and Skeletal Dysplasia”

Abstract

Low back pain is a global health problem with a markedly high lifetime prevalence— 70%–85% 1 —and socioeconomic burden—up to $102.0 billion/yr in the United States, 2 which is also the most common reason for the worker’s disability. 3 Although the cause of low back pain is largely nonspecific, a large-scale twin study has found intervertebral disc degeneration as the independent, main risk factor for disabling low back pain. 4 A population study of magnetic resonance imaging has further identified the increase in the prevalence of lumbar disc degeneration with age, based on 42% of 18–30 years and 88% of 50–55 years in age, 5 thereby facilitating impaired daily activities of the elderly. 6 Along with severe low back pain, intervertebral disc degeneration can cause neurological disorders such as ra-diculopathy, myelopathy, paralysis, intermittent claudication, and even bladder and bowel dysfunction. 7 Despite successful conservative treatment for degenerative disc disease, 6 non-responders need surgery. 7 The current primary surgical approach is symptomatic disc excision and/or spinal fusion, which results in the loss of load bearing, shock absorption, and movement. 7 Therefore, the development of new biological therapies for degenerative disc disease is an urgent demand to restore the physiological function. The intervertebral disc is unique, as the largest immune-privileged, low-nutrient, avascular organ in the human body. 8 The disc has a complex structure of the central nucleus pulp-osus (NP) encapsulated by the peripheral annulus fibrosus (AF) and sandwiching cartilage endplates. 7 The collagenous, laminar AF maintains the pressurization of the gelatinous, oval NP