Daniel Lajeunesse

• PhD
• Université de Montréal

Objective Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts (Ob) is involved in the progression and/or onset of osteoarthritis (OA). Human Ob isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/β-catenin signaling pathway (cWnt), and a reduced minera...

Supporting absolute data for LGR5 expression in normal and OA osteoblasts. (PZFX)

Supporting absolute data for effect of rhTGF-β on Wnt5a expression in OA osteoblasts. (PZFX)

Supporting absolute data for effect of rhWnt5a on TGF-β expression in OA osteoblasts. (PZFX)

Supporting absolute data for effect of siTGF-β on Wnt5a expression in OA osteoblasts. (PZFX)

Supporting absolute data for effect of siWnt5a on TGF-β expression in OA osteoblasts. (PZFX)

Supporting absolute data for effect of rhWnt5a on AP1 luciferase activity in OA osteoblasts. (PZFX)

Supporting absolute data for effect of rhWnt5a on NFAT luciferase activity in OA osteoblasts. (PZFX)

Effect of rhWnt5a treatments on AP-1 luciferase activity. AP-1 activity levels were measured with dual-luciferase reporter assay following rhWnt5a treatment in SaOS-2 cells (n = 3). (PDF)

Supporting absolute data for LGR4 expression in normal and OA osteoblasts. (PZFX)

Supporting absolute data for effect of siWnt5a on alizarin red staining in OA osteoblasts. (PZFX)

Effect of rhWnt5a treatments on NFAT luciferase activity. NFAT activity levels were measured with dual-luciferase reporter assay following rhWnt5a treatment in SaOS-2 cells (n = 4). (PDF)

Effect of rhWnt5a on SaOS-2 cells mineralization. Representative mineralization levels using ARS staining of SaOS-2 cells following rhWnt5a treatments for 10 days. (PDF)

Supporting absolute data for effect of siWnt5a on LGR4 expression in OA osteoblasts. (PZFX)

Supporting absolute data for effect of siWnt5a on LGR5 expression in OA osteoblasts. (PZFX)

Supporting absolute data for Wnt5a expression in normal and OA osteoblasts. (PZF)

Background Osteoarthritis (OA) is a complex disease, which affects multiple tissues, namely the subchondral bone, articular cartilage and synovial membrane. Alterations of the subchondral bone include an increased, yet under mineralized osteoid matrix, abnormal osteoblast cell phenotype including elevated alkaline phosphatase (ALP) activity, increa...

CARBOXYLATED AND UNCARBOXYLATED OSTEOCALCIN ARE NOT LINKED WITH INSULIN RESISTANCE IN OSTEOARTHRITIS PATIENTS. Abed, E., Mineau, F., Delorme, P., Martel-Pelletier, J., Pelletier, J.-P. & Lajeunesse, D. Unité de recherche en Arthrose, Centre de recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, Québec, Canada, H2X OA9...

Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising ther...

Sirtuins are widely distributed class III NAD+-dependent histone deacetylases (HDAC) involved in epigenetic regulation. There are seven protein members of the sirtuins, SIRT1-7, each of which specific sites of action linked with the intracellular localization, and acting on selective target proteins. Sirtuins are involved in a number of processes r...

Sirtuins are widely distributed class III NAD+-dependent histone deacetylases (HDAC) involved in epigenetic regulation. There are seven protein members of the sirtuins, SIRT1-7, each of which specific sites of action linked with the intracellular localization, and acting on selective target proteins. Sirtuins are involved in a number of processes r...

Purpose: Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts is involved in the progression of osteoarthritis (OA). Human osteoblasts isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/ß-catenin pathway, and a reduced mineralization in vitro as well...

Few studies have tried to discriminate a differential behavior between osteoarthritic (OA) osteoblasts (Obs). Based on osteocalcin level, we aimed, in the present study, to evaluate the capacity of OA Obs for producing molecules of the Wnt/β-catenin signaling pathway. Human primary OA Obs (n=11) were exposed or not to 50 nM of 1,25 dihydroxyvitamin...

IntroductionBone remodelling and increased subchondral densification are important in osteoarthritis (OA). Modifications of bone vascularisation parameters, which lead to ischemic episodes associated with hypoxic conditions, have been suspected in OA. Among several factors potentially involved, leptin and dickkopf-related protein 2 (DKK2) are good...

Background Clinical and in vitro studies suggest that subchondral bone is involved in the progression and/or onset of osteoarthritis (OA). Human osteoblasts (Obs) isolated from subchondral OA bone tissue show an altered phenotype and particularly produce higher level of leptin than normal human Obs. It has recently been demonstrated that Hif (hypox...

Objective To explore the disease-modifying effect, under therapeutic conditions, of strontium ranelate (SrRan) on the progression of joint structural changes and on the major pathophysiological pathways in an experimental osteoarthritis dog model. Methods Dogs underwent sectioning of the anterior cruciate ligament, and 4 weeks after surgery receive...

Abnormal osteogenesis in osteoarthritis: gone with the Wnt? Daniel Lajeunesse, Thomas F Chan, Aline Delalandre, Jean-Pierre Pelletier, Johanne Martel-Pelletier, and Élie Abed Background Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblast (Ob) functions, is involved in the progression and/or onset of ost...

Clinical and in vitro studies suggest that altered osteogenesis or bone remodeling is involved in the progression and/or onset of osteoarthritis (OA). Wnt signaling plays a key role in osteogenesis via the canonical Wnt/β-catenin signaling pathway. Two of the R-spondins, Rspo-1 and Rspo-2, a family of 4 proteins unrelated to other Wnt ligands that...

ABSTRACT The canonical Wnt/b-catenin signaling pathway (cWnt) plays a key role in osteogenesis and is reduced in human osteoarthritis (OA) osteoblasts (Ob). Sclerostin (SOST), a potent inhibitor of bone growth, alters cWnt, Sirtuin 1 (Sirt1) inhibits SOST expression in Ob, whereas SOST regulates the production of the Matrix extracellular phosphog...

The Wnt signaling pathway is crucial for osteogenesis and regulates terminal osteoblast differentiation. Although osteoarthritic (OA) osteoblasts show an abnormal phenotype and poor in vitro mineralization, the mechanism leading to this situation still remains unknow. Recent evidence indicates that Wnt signaling may be altered in OA osteoblasts. In...

The aim of this prospective, randomized, controlled, double-blind study was to evaluate the effects of tiludronate (TLN), a bisphosphonate, on structural, biochemical and molecular changes and function in an experimental dog model of osteoarthritis (OA). Baseline values were established the week preceding surgical transection of the right cranial/a...

A growing body of evidence suggests that the intimate link between the subchondral bone and overlying articular cartilage is not limited to physical contact but that physical and biochemical changes in one drive a response in the other. This chapter will review the fact that this intimate contact is not limited to biomechanical driven signals but e...

Osteoarthritis (OA) is associated with cartilage destruction, subchondral bone remodeling and inflammation of the synovial membrane, although the etiology and pathogenesis underlying this debilitating disease are poorly understood. Secreted inflammatory molecules, such as proinflammatory cytokines, are among the critical mediators of the disturbed...

Therapy (2010) 7(6), xxx–xxx Is there a role for bone tissue in osteoarthritis? Osteoarthritis (OA) is characterized by progres-sive articular cartilage loss, appositional new bone formation and sclerosis of the subchondral trabec-ulae and growth plate, formation of osteophytes, and an imbalance between loss of cartilage due to matrix degradation,...

In the context of translational research, there is growing interest in studying surgical orthopedic pain management approaches that are common to humans and dogs. The validity of postoperative pain assessment methods is uncertain with regards to responsiveness and the potential interference of analgesia. The hypothesis was that video analysis (as a...

Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integra...

Leptin is a peptide hormone with a role in bone metabolism and rheumatic diseases. The subchondral bone tissue plays a prominent role in the pathophysiology of osteoarthritis (OA), related to abnormal osteoblast (Ob) differentiation. Although leptin promotes the differentiation of Ob under normal conditions, a role for leptin in OA Ob has not been...

The human osteosarcoma cell line MG-63 has been used to study the production of the bone-specific protein, osteocalcin. In the absence of any stimuli, MG-63 cells secreted very low levels of osteocalcin. The secretion of osteocalcin started after a lag time of 10-12 h upon 1,25-(OH)2D3 treatment. Osteocalcin secretion was measured at doses as low a...

Earlier studies suggest the involvement of osteoprotegerin (OPG), RANK and RANK ligand (RANKL) in OA subchondral bone metabolism; however, few studies have looked at their functional consequences on chondrocytes. We compared the expression/production of OPG, RANK and RANKL on human normal and OA chondrocytes, and evaluated, on OA chondrocytes, thei...

Bone tissue in osteoarthritis (OA) is composed of abundant undermineralized osteoid matrix. The aim of this study was to investigate the mechanisms responsible for this abnormal matrix, using in vitro OA subchondral osteoblasts. Primary normal and OA osteoblasts were prepared from tibial plateaus. Phenotype was determined by alkaline phosphatase ac...

In osteoarthritis (OA), the subchondral bone undergoes a remodelling process involving several factors synthesized by osteoblasts. In this study, we investigated the expression, production, modulation, and role of PAR-2 in human OA subchondral bone osteoblasts. PAR-2 expression and production were determined by real-time PCR and flow cytometry, res...

Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having pro...

Background: Osteoarthritis (OA) is the most common human joint disease. Recent studies suggest that an abnormal subchondral bone metabolism is intimately involved in the genesis of this disease. Bone remodelling is tightly regulated by a molecular triad composed of OPG/RANK/RANKL. RANKL exists as 3 isoforms: RANKL1, 2, and 3. RANKL1 and 2 enhance...

We previously reported that human OA subchondral bone osteoblasts could be discriminated into two subpopulations identified by their levels of endogenous production (low [L] or high [H]) of PGE(2). Here, we investigated the OPG and RANKL expression levels, the histologic analysis of the subchondral bone as well as the osteoclast differentiation eff...

In osteoclastogenesis, the intercellular adhesion molecule (ICAM)-1 provides a high-affinity adhesion between the osteoblast and the osteoclast precursor, thereby facilitating the interaction between receptor activator nuclear factor kappaB ligand (RANKL) and its receptor RANK. However, the role of soluble ICAM (sICAM) in that process remains obscu...

Early in the pathological process of osteoarthritis (OA), subchondral bone remodelling, which is related to altered osteoblast metabolism, takes place. In the present study, we explored in human OA subchondral bone whether chondroitin sulfate (CS), glucosamine sulfate (GS), or both together affect the major bone biomarkers, osteoprotegerin (OPG), r...

A figure showing p42/44 levels and activation in normal and osteoarthitis (OA) osteoblasts. Cells were grown to confluence and incubated overnight in serum free medium. Cells were then exposed to 50 ng/ml insulin-like growth factor (IGF)-1 for 15 minutes. Phospho p42/44 levels were detected by westen blot analysis. The figure shows a representative...

A figure showing phospho-protein kinase B (pPKB) and phosphatidylinositol 3-kinase (PI3K) levels and activation in normal and osteoarthitis (OA) osteoblasts. Cells were grown to confluence and incubated overnight in serum free medium. Cells were then exposed to 50 ng/ml insulin-like growth factor (IGF)-1 for 5 minutes. The top panel shows a represe...

Human osteoarthritis (OA) is characterized by cartilage loss, bone sclerosis, osteophyte formation and inflammation of the synovial membrane. We previously reported that OA osteoblasts (Ob) show abnormal phenotypic characteristics possibly responsible for bone sclerosis and that two subgroups of OA patients can be identified by low or high endogeno...

Osteoarthritis is considered an illness in which a complex interaction between the tissues of the joint plays a significant role in the initiation and/or progression of this pathophysiology. We do not yet completely understand all the factors that are responsible for initiating the degradation and loss of the articular tissues. This paper summarize...

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discrim...

Insulin-like growth factor (IGF)-1 is a key factor in bone homeostasis and could be involved in bone tissue sclerosis as observed in osteoarthritis (OA). Here, we compare the key signaling pathways triggered in response to IGF-1 stimulation between normal and OA osteoblasts (Obs). Primary Obs were prepared from the subchondral bone of tibial platea...

To determine trabecular and subchondral bone metabolic changes in experimental canine osteoarthritis (OA). OA was induced in 19 dogs by transection of the anterior cruciate ligament (ACL) of the right knee through a stab wound. Dogs were sacrificed at 8 (n=7) and 12 weeks (n=12) after surgery. Non-operated normal dogs (n=6) were used as controls. A...

Bone diseases such as osteoporosis, osteoarthritis and rheumatoid arthritis (RA) affect a great proportion of individuals, with debilitating consequences in terms of pain and progressive limitation of function. Existing treatment of these pathologies has been unable to alter the natural evolution of the disease and, as such, a clearer understanding...

This study sought to evaluate the levels of mRNA expression and protein synthesis of MMP-13, cathepsin K, aggrecanase-1 (ADAMTS-4), aggrecanase-2 (ADAMTS-5) and 5-lipoxygenase (5-LOX) in cartilage in the experimental anterior cruciate ligament (ACL) dog model of osteoarthritis (OA), and to examine the effects of treatment with licofelone, a 5-lipox...

To describe the pattern of expression of intercellular adhesion molecule-1 (ICAM-1) at the surface of human osteoblasts (Ob) recovered from normal (control), osteoporotic (OP), and osteoarthritic (OA) bone. To relate ICAM-1 expression in OA Ob with interleukin-6 (IL-6) and prostaglandin E2 (PGE2) production. Trabecular bone specimens were taken fro...

To compare the effects of polymethylmetacrylate (PMMA), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) on osteoarthritic (OA) human osteoblasts (Ob). Ob cell cultures were prepared from metaphyseal trabecular bone of OA patients (n=9). Their cellular metabolic activity was characterized by measuring a...

To evaluate the morphological changes that take place in the subchondral bone and calcified cartilage zone in the experimental anterior cruciate ligament (ACL) dog model of osteoarthritis (OA) and analyze concomitant changes in the level of MMP-13 and cathepsin K, as well as examine the therapeutic effects of licofelone, a lipoxygenase (LO)/cycloox...

Bone, and especially the subchondral bone plate, is involved in the pathogenesis of osteoarthritis (OA). OA bone tissue is sclerotic yet undermineralized indicating abnormal bone cell metabolism. Studies in both human and animal models of OA support the concept that bone sclerosis could precede cartilage degradation and loss. Clinical studies show...

To determine if treatment with licofelone, a combined 5-lipoxygenase and cyclo-oxygenase inhibitor, in vivo in experimental dog osteoarthritis can modify bone cell metabolism in long term in vitro subchondral osteoblast cell cultures (Ob). Group 1 received sectioning of the anterior cruciate ligament (ACL) of the right knee with no active treatment...

The underlying mechanisms responsible for both cartilage loss and subchondral bone changes in osteoarthritis (OA) remain unknown. It is becoming recognized that the extracellular matrix influences the metabolism of cells both in vivo and in vitro and can modify their responses to external stimuli. Indeed, the glycosaminoglycan/proteoglycan matrix i...

This review deals with new findings highlighting the concept of cross-talk between subchondral bone tissue and articular cartilage that may be crucial for the initiation and/or progression of osteoarthritis. In this review, new factors either produced by subchondral bone tissue or modifying osteoblast metabolism, yet implicated in osteoarthritis, a...

HGF is increased in human OA cartilage, possibly from Ob's. RT‐PCR shows HGF isoforms are differently regulated between chondrocytes and Ob. A paracrine cross‐talk between subchondral bone and cartilage may occur during OA. Recently, hepatocyte growth factor (HGF) has been identified by immunohistochemistry in cartilage and more particularly in the...

Dual 5-LOX/COX inhibitors are potential new drugs to treat inflammation. They act by blocking the formation of both prostaglandins and leucotrienes but do not affect lipoxin formation. Such combined inhibition avoids some of the disadvantages of selective COX-2 inhibitors and spares the gatrointestinal mucosa.

Abstract Osteoarthritis (OA) is considered to be a complex illness in which the tissues of the joint play a significant role in the initiation and/or progression of the pathophysiology. We still do not completely understand what initiates the degradation and loss of cartilage. However, it has been suggested that increased catabolism due to elevated...

In summary, OA osteoblasts show a number of metabolic alterations that may interfere with normal cell metabolism and signaling, possibly leading to altered extracellular matrix composition and function. In turn, such changes in cellular events may lead to abnormal cross talk between cells from the subchondral bone plate and articular cartilage lead...

We investigated whether the absence of Phex (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) in the Hyp mouse affects the expression and activity of neprilysin (NEP) and of endothelin-converting enzyme-like endopeptidase (ECEL1/DINE) in bone marrow stromal cells (BMSC) and osteoblasts (Ob). Total NEP-like activity w...