Platelet-Derived Growth Factor B Is a Key Element in the Pathological Bone Formation of Ankylosing Spondylitis

Abstract

Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet-derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC). Human entheseal tissues attached to facet joints or spinous processes were harvested at the time of surgery and investigated for bone-forming activity. The impact of a pharmacological agonist and antagonist of platelet-derived growth factor B receptor (PDGFRB) were investigated respectively in curdlan-treated SKG mice. PDGFB levels were elevated in AS sera and correlated with radiographic progression of AS in the spine. Mature osteoclasts secreting PDGFB proteins were increased in the AS group compared with HC and were observed in bony ankylosis tissues of AS. Expression of PDGFRB was significantly elevated in the spinous enthesis and facet joints of AS compared with controls. Moreover, recombinant PDGFB treatment accelerated bone mineralization of enthesis cells, which was pronounced in AS, whereas PDGFRB inhibition efficiently reduced the PDGFB-induced bone mineralization. Also, PDGFRB inhibition attenuated the severity of arthritis and enthesophyte formation at the joints of curdlan-treated SKG mice. This study suggests that regulating PDGFB/PDGFRB signaling could be a novel therapeutic strategy to block key pathophysiological processes of AS.

Differentially expressed protein‐coding genes in ankylosing spondylitis: Emerging insights into pathogenesis and therapeutic approaches

“…Moreover, recombinant PDGFB administration enhanced enthesis cells' bone mineralization, which was evident in AS, whereas PDGFRB inhibition effectively inhibited PDGFB's capacity to trigger bone mineralization. A potential suppression of bone growth in AS may commence with pharmacological targeting of PDGFRB 131,132 . It was reported that the Wnt pathway contributes to both homeostasis and bone formation.…”

“…A potential suppression of bone growth in AS may commence with pharmacological targeting of PDGFRB. 131,132 It was reported that the Wnt pathway contributes to both homeostasis and bone formation.…”

Extracellular PPM1A promotes mineralization of osteoblasts differentiation in ankylosing spondylitis via the FOXO1A‐RUNX2 pathway

“…The protocols for isolation of osteoprogenitor cells were previously reported 26–31 . Surgical bone were split into pieces using rongeur, followed by washed with 1× PBS supplemented with 1% penicillin and streptomycin (Gibco, 15140122) to remove all marrow cells and blood.…”

“…The protocols for isolation of osteoprogenitor cells were previously reported. [26][27][28][29][30][31] Surgical bone were split into pieces using rongeur, followed by washed with 1× PBS supplemented with 1% penicillin and streptomycin (Gibco, 15140122) to remove all marrow cells and blood. The bone tissue were cultured in DMEM-HG (Hyclone, SH30243.01) supplemented with 10% FBS (Gibco, 16000044) and 1% penicillin and streptomycin (Gibco, 15140122) at 37°C in 5% CO 2 conditioned incubators.…”

LINC00323 induced by hypoxia promote cartilage callus by interacting with FUS to regulate PDGFB expression

“…3A). Previous studies have shown that PDGFB was known to be a potent mitogen and chemoattractant for cells involved in wound healing and tissue regeneration, including cells critical for bone healing processes [24,25]. Then, PDGFB was chosen for further investigation.…”