PLAP-1/Asporin, a Novel Negative Regulator of Periodontal Ligament Mineralization

Abstract

Periodontal ligament-associated protein-1 (PLAP-1)/asporin is a recently identified novel member of the small leucine-rich repeat proteoglycan family. PLAP-1/asporin is involved in chondrogenesis, and its involvement in the pathogenesis of osteoarthritis has been suggested. We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells. In situ hybridization analysis revealed that PLAP-1/asporin was expressed specifically not only in the PDL of an erupted tooth but also in the dental follicle, which is the progenitor tissue of the PDL during tooth development. Overexpression of PLAP-1/asporin in mouse PDL-derived clone cells interfered with both naturally and bone morphogenetic protein 2 (BMP-2)-induced mineralization of the PDL cells. On the other hand, knockdown of PLAP-1/asporin transcript levels by RNA interference enhanced BMP-2-induced differentiation of PDL cells. Furthermore co-immunoprecipitation assays showed a direct interaction between PLAP-1/asporin and BMP-2 in vitro, and immunohistochemistry staining revealed the co-localization of PLAP-1/asporin and BMP-2 at the cellular level. These results suggest that PLAP-1/ asporin plays a specific role(s) in the periodontal ligament as a negative regulator of cytodifferentiation and mineralization probably by regulating BMP-2 activity to prevent the periodontal ligament from developing non-physiological mineralization such as ankylosis.

miR-21 and miR-101 regulate PLAP-1 expression in periodontal ligament cells

“…Moreover, PLAP-1 was not only expressed specifically in the PDL of an erupted tooth but also in the dental follicle, which is the progenitor tissue of the PDL during tooth development (8). This result suggests that PLAP-1 may be involved in PDL development and cytodifferentiation (11).…”

“…Periodontal ligament associated protein-1 (PLAP-1/ asporin), a specific marker of the PDL, is an important negative regulator of osteogenic differentiation in maintaining the homeostasis of periodontium (6)(7)(8). PLAP-1 was first identified as a novel member of the small leucine-rich repeat proteoglycan (SLRP) family and confirmed to be expressed specifically and predominantly in the PDL (9-10).…”

Simple replantation protocol to avoid ankylosis in teeth intended for orthodontic treatment

“…It also plays as a negative regulator of cytodifferentiation and mineralization probably by regulating BMP-2 activity to prevent the PDL from developing non-physiological mineralization such as ankylosis. 8 …”

“…Therefore, the benefit of early detection is that it gives earlier warning of growthassociated infraocclusion. 2,3,7,8 …”

“…8 Necrosis of the periodontal ligament's cellular elements by desiccation, crushing or mechanical damage, as in severe luxation injury, disrupts this normal homeostatic mechanism. Ankylosis is established not only via inflammatory-mediated and mechanical alterations in the periodontal ligament but also because insufficient functional cellular elements survive to suppress osteogenic activity.…”