WISP1/CCN4 aggravates cartilage degeneration in experimental osteoarthritis.

Increased Wisp1 expression was previously reported in experimental and human osteoarthritis (OA). Moreover, adenoviral overexpression of Wisp1 in naïve mouse knee joints resulted in early OA-like cartilage lesions. Here, we determined how the matricellular protein WISP1 is involved in the pathology that occurs in the complex osteoarthritic environment with aging and experimental OA in wild type (WT) and Wisp1-/- mice. WT and Wisp1-/- mice were aged or experimental OA was induced with intraarticular collagenase injection, destabilization of the medial meniscus (DMM) or anterior cruciate ligament transection (ACLT). Joint pathology was assessed using histology and microCT. Protease expression was evaluated with qRT-PCR and activity was determined by immunohistochemical staining of the aggrecan neoepitope NITEGE. Protease expression in human end-stage OA synovial tissue was determined with qRT-PCR after stimulation with WISP1. With aging, spontaneous cartilage degeneration in Wisp1-/- was not decreased compared to their WT controls. However, we observed significantly decreased cartilage degeneration in Wisp1-/- mice after induction of three independent experimental OA models. While the degree of osteophyte formation was comparable between WT and Wisp1-/- mice, increased cortical thickness and reduced trabecular spacing was observed in Wisp1-/- mice. In addition, we observed decreased MMP3/9 and ADAMTS4/5 expression in Wisp1-/- mice, which was accompanied by decreased levels of NITEGE. In line with this, stimulation of human OA synovium with WISP1 increased the expression of various proteases. WISP1 plays an aggravating role in the development of post-traumatic experimental OA.

van den Bosch MH ，Blom AB ，Kram V ，Maeda A ，Sikka S ，Gabet Y ，Kilts TM ，van den Berg WB ，van Lent PL ，van der Kraan PM ，Young MF ... -  《-》

Induction of Canonical Wnt Signaling by Synovial Overexpression of Selected Wnts Leads to Protease Activity and Early Osteoarthritis-Like Cartilage Damage.

Proteins from the Wnt signaling pathway are very important for joint development. Curiously, osteoarthritis (OA) is thought to be a recapitulation of developmental processes. Various members of the Wnt signaling pathway are overexpressed in the synovium during experimental OA. Here, we investigated the potency of specific Wnt proteins, when expressed in the synovium, to induce OA pathology. We overexpressed Wnt5a, Wnt8a, Wnt16, and WISP1 in the synovium using adenoviral vectors. We determined whether overexpression resulted in OA pathology by histology, and we measured whether Wnt signaling led to increased protease activity in the joint. Synovial overexpression of Wnt8a and Wnt16 led to canonical Wnt signaling in the cartilage, whereas overexpression of Wnt5a did not. Canonical Wnt signaling increased protease activity and induced cartilage damage shortly after overexpression. Specific blocking of the canonical Wnt signaling pathway with Dickkopf-1 reduced the Wnt-signaling-induced cartilage damage. By contrast, the noncanonical signaling Wnt5a did not cause cartilage lesions. Overexpression of WISP1, a downstream protein of canonical Wnt signaling, resulted in increased cartilage damage. In conclusion, our data show that canonical Wnts and WISP1, which we found overexpressed in the synovium during experimental OA, may conduce to OA pathology.

van den Bosch MH ，Blom AB ，Sloetjes AW ，Koenders MI ，van de Loo FA ，van den Berg WB ，van Lent PL ，van der Kraan PM ... -  《-》

Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1.

Blom AB ，Brockbank SM ，van Lent PL ，van Beuningen HM ，Geurts J ，Takahashi N ，van der Kraan PM ，van de Loo FA ，Schreurs BW ，Clements K ，Newham P ，van den Berg WB ... -  《-》

Early and stable upregulation of collagen type II, collagen type I and YKL40 expression levels in cartilage during early experimental osteoarthritis occurs independent of joint location and histological grading.

Lorenz H ，Wenz W ，Ivancic M ，Steck E ，Richter W ... -  《-》

Chaperonin 60 regulation of SOX9 ubiquitination mitigates the development of knee osteoarthritis.

Ko JY ，Sun YC ，Li WC ，Wang FS ... -  《-》