Painful temporomandibular joint overloading induces structural remodeling in the pericellular matrix of that joint's chondrocytes

Franklin, Melissa; Sperry, Megan M.; Phillips, Evan R.; Granquist, Eric J.; Marcolongo, Michele; Winkelstein, Beth A.

doi:10.1002/jor.25050

Cited by 8 publications

(6 citation statements)

References 55 publications

(120 reference statements)

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“…Detailed investigations of the pericellular matrix surrounding chondrocytes within the TMJ cartilage following loading showed that collagen VI increased in both the 2 N and 3.5 N groups, whereas there was a greater increase in aggrecan non-epitopes in the 3.5 N group. These results suggest that aggrecan fragmentation may be relevant to pain responses and the severity of structural damage to the TMJ ( 126 ).…”

Section: Preclinical Studies For Tmjoa and Pain From Tmjmentioning

confidence: 96%

The degeneration-pain relationship in the temporomandibular joint: Current understandings and rodent models

et al. 2023

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Temporomandibular disorders (TMD) represent a group of musculoskeletal conditions involving the temporomandibular joints (TMJ), the masticatory muscles and associated structures. Painful TMD are highly prevalent and conditions afflict 4% of US adults annually. TMD include heterogenous musculoskeletal pain conditions, such as myalgia, arthralgia, and myofascial pain. A subpopulations of TMD patients show structural changes in TMJ, including disc displacement or degenerative joint diseases (DJD). DJD is a slowly progressing, degenerative disease of the TMJ characterized by cartilage degradation and subchondral bone remodeling. Patients with DJD often develop pain (TMJ osteoarthritis; TMJ OA), but do not always have pain (TMJ osteoarthrosis). Therefore, pain symptoms are not always associated with altered TMJ structures, which suggests that a causal relationship between TMJ degeneration and pain is unclear. Multiple animal models have been developed for determining altered joint structure and pain phenotypes in response to various TMJ injuries. Rodent models of TMJOA and pain include injections to induce inflammation or cartilage destruction, sustained opening of the oral cavity, surgical resection of the articular disc, transgenic approaches to knockout or overexpress key genes, and an integrative approach with superimposed emotional stress or comorbidities. In rodents, TMJ pain and degeneration occur during partially overlapping time periods in these models, which suggests that common biological factors may mediate TMJ pain and degeneration over different time courses. While substances such as intra-articular pro-inflammatory cytokines commonly cause pain and joint degeneration, it remains unclear whether pain or nociceptive activities are causally associated with structural degeneration of TMJ and whether structural degeneration of TMJ is necessary for producing persistent pain. A thorough understanding of the determining factors of pain-structure relationships of TMJ during the onset, progression, and chronification by adopting novel approaches and models should improve the ability to simultaneously treat TMJ pain and TMJ degeneration.

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Section: Preclinical Studies For Tmjoa and Pain From Tmjmentioning

confidence: 96%

The degeneration-pain relationship in the temporomandibular joint: Current understandings and rodent models

et al. 2023

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“…Eventually, buckling during normal valve opening initiates tears that propagate and cause valve failure. 21 Our lab has synthesized and characterized a family of synthetic proteoglycan analogs, [22][23][24][25][26][27][28] termed biomimetic proteoglycans (BPGs).…”

Section: Introductionmentioning

confidence: 99%

“…Our lab has synthesized and characterized a family of synthetic proteoglycan analogs, 22–28 termed biomimetic proteoglycans (BPGs). BPGs have a linear poly(acrylic acid) (PAA) backbone whose length can be tuned, enabling synthesis of BPGs of varying size.…”

Section: Introductionmentioning

confidence: 99%

Biomimetic proteoglycans as a tool to engineer the structure and mechanics of porcine bioprosthetic heart valves

Petrovic,

Kahle,

Han

et al. 2023

J Biomed Mater Res

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The utility of bioprosthetic heart valves (BHVs) is limited to certain patient populations because of their poor durability compared to mechanical prosthetic valves. Histological analysis of failed porcine BHVs suggests that degeneration of the tissue extracellular matrix (ECM), specifically the loss of proteoglycans and their glycosaminoglycans (GAGs), may lead to impaired mechanical performance, resulting in nucleation and propagation of tears and ultimately failure of the prosthetic. Several strategies have been proposed to address this deterioration, including novel chemical fixatives to stabilize ECM constituents and incorporation of small molecule inhibitors of catabolic enzymes implicated in the degeneration of the BHV ECM. Here, biomimetic proteoglycans (BPGs) were introduced into porcine aortic valves ex vivo and were shown to distribute throughout the valve leaflets. Incorporation of BPGs into the heart valve leaflet increased tissue overall GAG content. The presence of BPGs also significantly increased the micromodulus of the spongiosa layer within the BHV without compromising the chemical fixation process used to sterilize and strengthen the tissue prior to implantation. These findings suggest that a targeted approach for molecularly engineering valve leaflet ECM through the use of BPGs may be a viable way to improve the mechanical behavior and potential durability of BHVs.

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“…19,22,45 Animal studies showed that activated osteoclasts may also induce sensory innervation and pain in OA. 13,37,45 Thus, interventions that reduce subchondral bone remodeling may be beneficial to protect against cartilage degradation and attenuate OA pain. 19 Many clinicians prescribe nonpharmacologic methods, such as exercise and walking, for patients with OA as first-line treatment according to the 2019 guidelines of…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Axial Compressive Loading Attenuates Early Osteoarthritis by Reducing Subchondral Bone Remodeling

Pan

et al. 2023

Am J Sports Med

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Background: Mechanical loading and alendronate (ALN) can be used as noninvasive physical therapy methods for osteoarthritis (OA). However, the timing and efficacy for treatments are unknown. Purpose: To determine whether the timing of mechanical loading and ALN influences the pathobiological changes of OA. Study Design: Controlled laboratory study. Methods: Mice with OA induced by anterior cruciate ligament transection were subjected to early (1-3 weeks) or late (5-7 weeks) axial compressive dynamic load or intraperitoneal injection of ALN. Changes in gait were analyzed using gait analysis system, pathobiological changes in subchondral bone, cartilage, osteophyte, and synovitis were assessed using micro–computed tomography, tartrate-resistant acid phosphatase staining, pathologic section staining, and immunohistochemistry at 1, 2, 4, and 8 weeks. Results: At 1, 2, and 4 weeks, the OA limb had lower mean footprint pressure intensity, lower bone volume per tissue volume (BV/TV) in the subchondral bone, and more osteoclasts. At 4 weeks, the early loading, ALN, and load + ALN treatments induced less cartilage destruction, with a corresponding reduction in Osteoarthritis Research Society International score and increased hyaline cartilage thickness. The treatments also resulted in fewer osteoclasts and higher BV/TV and bone mineral density of subchondral bone and suppressed inflammation and interleukin 1β– and tumor necrosis factor α-positive cells in synovium. At 8 weeks, early loading or load + ALN improved the mean footprint pressure intensity and knee flexion. At 8 weeks, early load + ALN had a synergistic effect on protecting hyaline cartilage and proteoglycans. Footprint pressure intensity and cartilage destruction were worse in late loading limbs, and no differences in BV/TV, bone mineral density, osteophyte formation, and synovium inflammation were found between the late load, ALN, and load + ALN groups and the anterior cruciate ligament transection group. Conclusion: Dynamic axial mechanical loading or ALN in the early stages of knee trauma protected against OA by suppressing subchondral bone remodeling. However, late loading promoted cartilage degeneration in advanced OA, indicating that reduced loading should be performed in the late stages of OA to avoid the acceleration of OA. Clinical Relevance: Early low-level functional exercise or antiosteoporotic drugs could clearly slow or prevent the progression of early OA. For patients with mild to severe OA, loading reduction via brace protection or maintenance of joint stability via early ligament reconstruction surgery may ameliorate OA exacerbation.

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Painful temporomandibular joint overloading induces structural remodeling in the pericellular matrix of that joint's chondrocytes

Cited by 8 publications

References 55 publications

The degeneration-pain relationship in the temporomandibular joint: Current understandings and rodent models

The degeneration-pain relationship in the temporomandibular joint: Current understandings and rodent models

Biomimetic proteoglycans as a tool to engineer the structure and mechanics of porcine bioprosthetic heart valves

Axial Compressive Loading Attenuates Early Osteoarthritis by Reducing Subchondral Bone Remodeling

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