Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint

Version 1 : Received: 21 June 2021 / Approved: 23 June 2021 / Online: 23 June 2021 (11:07:01 CEST)

How to cite: Zhang, Z.; Lu, L.; Ye, T.; Yu, S.; Zhang, J.; Zhang, M.; He, F.; Liu, Q.; Feng, J.; Yang, H. Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint. Preprints 2021, 2021060566 (doi: 10.20944/preprints202106.0566.v1). Zhang, Z.; Lu, L.; Ye, T.; Yu, S.; Zhang, J.; Zhang, M.; He, F.; Liu, Q.; Feng, J.; Yang, H. Inhibition of Semaphorin 4D/Plexin-B1 Signal Inhibits the Subchondral Bone Loss in Early-Stage Osteoarthritis of Temporomandibular Joint. Preprints 2021, 2021060566 (doi: 10.20944/preprints202106.0566.v1).

Abstract

Subchondral bone loss is an important pathological feature of early-stage temporomandibular joint (TMJ) osteoarthritis (OA). Previous studies focused mainly on the bone resorption by osteoclasts in early-stage OA, but the bone formation feature has not drawn enough attention. Sema4D/Plexin-B1 is a pair of molecules expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblasts. The present study found that subchondral bone loss in early-stage TMJ OA was accompanied by up-regulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D level could inhibit the subchondral bone loss and cartilage degeneration of early-stage TMJ OA. In vitro, results revealed that Sema4D could reduce the expression of osteocalcin (OCN) and alkaline phosphatase (ALP), and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ OA might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in the early-stage OA holds promise as a strategy for new therapeutic approaches to osteoarthritis.

Keywords

Temporomandibular joint; Osteoarthritis; Semaphorin 4D; Plexin-B1; Osteoblast

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