Chapter 6

1. Chapter 6 Bones and Skeletal Tissues J.F. Thompson, Ph.D. & J.R. Schiller, Ph.D. & G. Pitts, Ph.D.

2. Functions of Bones • Support – a framework for the body • Protection • bones protect many internal organs • cranial bones surround the brain; vertebrae surround the spinal cord; pelvic girdle surrounds the reproductive organs • Movement - muscles attach to bones • Mineral homeostasis - Ca++, PO-4 storage • Site of blood cell production - hematopoiesis in red bone marrow

4. Macroscopic Bone Structure • Diaphysis • the shaft of a long bone • contains medullary or marrow cavity • infants have considerable red (hematopoietic) bone marrow • red marrow is gradually replaced by yellow (fatty) bone marrow throughout life • Epiphysis (epiphyses) • ends of a long bone • epiphyseal plate - growth plate made of cartilage • nutrient foramen - site of blood vessel entry into bone • articular cartilage - hyaline cartilage covering epiphysis

5. Periosteum • Two layers of connective tissue around bone • Fibrous layer (outer) - dense irregular connective tissue • Osteogenic layer (inner) • osteoblasts – bone-forming cells • osteoclasts – bone-remodeling cells • Perforating (Sharpey’s) fibers (collagen) anchor periosteum to the bone • Site of ligament, tendon attachment • Large supply of nerves & blood vessels

6. Endosteum • lines the medullary cavity • has osteogenic layer only • contains osteoblasts and osteoclasts

7. Bone Tissue Histology • Much intercellular matrix (osteoid) • Matrix mineralized • 25% water • 25% protein fibers • 50% hydroxyapatites (calcium phosphate) salts

8. Osteoblasts and Osteocytes • Osteoblasts - bone forming cells • Secrete collagen and other organic components for bone synthesis • Found on any bone surface • Osteocytes - mature bone cells • Embedded in matrix in lacunae with canaliculi • Maintain daily activities of bone tissue; nutrient, waste exchange

9. Osteoclasts • Osteoclasts • settle on bone surface • function in bone resorption (matrix destruction) for growth, development, maintenance, repair

10. Histology of Bone Tissue • Maturation • matrix secretion – ground substance & collagen • crystallization = calcification = mineralization • hydroxyapatite (calcium phosphate salt) • other salts • hardness vs. flexibility • collagen fibers • mineralization • crystallization develops around collagen fibers • stronger than egg shells which have no collagen • matrix is not continuous, because many vascular passageways penetrate the mineralized matrix • size and distribution of these vascular channels determines the type of bone - spongy or compact

11. Types of Bone • Compact • Appears very dense • Most of the bone mass in the body • Spongy • Small struts of bone (trabeculae) • May appear randomly organized, but the trabeculae, like girders in a building, are generally oriented in the directions of stresses

12. Compact Bone - Osteons • Blood vessels run through perforating (Volkman’s) canals to the central (Haversian) canals

13. Compact Bone - Osteons • Osteon - central canal with lamellae, lacunae, osteocytes, & canaliculi • osteocytes in lacunae • canaliculi – house cytoplasmic extensions from the osteocytes, so they are in contact for transport and communication

14. Compact Bone - Interstitial Lamellae • found in older bone • older osteons are gradually broken down and replaced during the remodeling process

15. Compact Bone – Microscopic View

16. Spongy Bone • No true osteon systems – osteoblasts produce an irregular strutwork of trabeculae • Osteocytes receive nutrients by diffusion through canaliculi • Red marrow (1) fills the spaces between the trabeculae (2) (hematopoietic marrow) • Blood vessels pass through compact bone to spongy bone • Blood vessels pass through yellow marrow cavities; open out to become red marrow cavities

17. The Early Embryonic Skeleton Bone develops later→ • embryonic skeleton – composed of fibrous connective tissue membranes and hyaline cartilage

18. Bone Formation and Growth • Ossification/osteogenesis • Begins at week 4 of development • There are two different types of bone formation • Each process leads to the formation of mature compact and spongy bones • Fibrous membrane model - intramembranous ossification – “membrane bones” • Hyaline cartilage model - endochondral ossification • the initial cartilage is transformed to become “endochondral bones”

19. Intramembranous Ossification • Results in the formation of cranial bones and the clavicles. • All are flat bones • At the site of bone development • Ossification begins in fibrous connective tissue membranes formed by mesenchymal cells. • Osteoprogenitor cells (osteoblasts): clusters of embryonic cells • become centers of ossification, secrete matrix until they are surrounded

20. Intramembranous Ossification • As the matrix forms, trabeculae form, joining together, forming the lattice of spongy bone • Outside vascularized connective tissue develops into the periosteum • Bone collar of compact bone forms, and red marrow appears • Most of this bone will be remodeled into compact bone over time

21. Intramembranous Ossification - 1

22. Intramembranous Ossification -2

23. Intramembranous Ossification - 3

24. Intramembranous Ossification - 4

25. Endochondral Ossification • begins in the second month of development • forms all bones below the base of the skull (except clavicle) • uses hyaline cartilage models for bone development • requires breakdown of hyaline cartilage prior to ossification • begins in the primary ossification center • the perichondrium covering the hyaline cartilage is infiltrated by blood vessels, converting it to a vascularized periosteum • increased nutritional status allows mesenchymal cells to specialize into osteoblasts , creating the primary ossification center, and a vascularized endosteum

26. Stages of Endochondral Ossification • formation of bone collar • cavitation of the hyaline cartilage • invasion of internal cavities by the periosteal bud, and spongy bone formation • formation of the medullary cavity; appearance of secondary ossification centers in the epiphyses • ossification of the epiphyses, with hyaline cartilage remaining only in the epiphyseal plates

27. Endochondral Ossification – 1 Formation of bone collar • osteoblasts secrete osteoid against the hyaline cartilage of the diaphysis

28. Endochondral Ossification – 2 Cavitation of the hyaline cartilage • chondrocytes in the diaphysis hypertrophy and start to calcify the surrounding cartilage matrix • chondrocytes die and matrix deteriorates • cavities open • cartilage growth continues

29. Endochondral Ossification – 3 • Invasion of internal cavities by the periosteal bud, and spongy bone formation • 3 months of age • Cavities are invaded by periosteal bud • Osteoclasts partially erode the cartilage matrix • Osteoblasts secrete osteoid around remaining cartilage matrix , forming spongy bone

30. Endochondral Ossification – 4 Diaphysis elongation and formation of the medullary cavity; appearance of secondary ossification centers in the epiphyses • Osteoclasts breakdown new spongy bone, opening the medullary cavity. • Cartilage growth continues at epiphyseal plate • Ossification chases cartilage formation • Secondary ossification centers arise in the epiphysis shortly before/after birth

31. Endochondral Ossification – 5 Ossification of the epiphyses, with hyaline cartilage remaining only in the epiphyseal plates • the epiphyses gain bony tissue, compact bone at the surfaces, spongy bone in the interior • chondroblasts secrete matrix until they are embedded • chondrocytes and matrix begin to disintegrate • osteoclasts invade to remove cartilage matrix • osteoblasts form bony matrix, trabeculae form, joining together, forming the lattice of spongy bone • when complete, hyaline cartilage remains only at the epiphyseal plate and the articular cartilages • continues through childhood and adolescence

32. Postnatal Bone Growth

33. Postnatal Bone Growth • Regulated by hGH and the sex hormones • In children, cartilage production continues on the epiphyseal (distal) side • cells are destroyed & replaced to increase the length of bone • plate fracture increases calcification; ends growth in length • growth ceases • bone shows epiphyseal lines • clavicle is the last bone to stop growing • generally complete by age 25 • lengthwise growth completed earlier in women

34. Postnatal Long Bone Growth • Growth in length of long bones • Cartilage on the side of the epiphyseal plate next to the epiphysis is relatively inactive • Cartilage adjacent to the shaft of the bone organizes into a pattern that allows for fast, efficient cartilage growth

35. Postnatal Long Bone Growth • chondrocytes in the growth zone divide quickly, pushing the epiphysis away from the diaphysis • older chondrocytes in the hypertrophic zone swell, causing their lacunae to erode and enlarge • cartilage matrix calcifies and the chondrocytes die • this leaves long spicules of calcified cartilage at the epiphysis-diaphysis junction

36. Postnatal Long Bone Growth • the spicules become the osteogenic zone which is invaded by marrow cells from the endosteum beneath • the spiculues of calcified cartilage are removed by osteoclasts • osteoblasts secrete new bone matrix to form new spongy bone

37. Long Bone Growth • At the end of adolescence, epiphyseal plate chondrocytes divide less often and the remaining hyaline cartilage of the epiphyseal plates is replaced by bone tissue • Epiphyseal Plate Closure: longitudal growth ceases and the epiphyses/diaphysis fuse. • females at 18 years; males at 21 years • the clavicle is the last bone to stop growing

38. Appositional Bone Growth • Growth in width • from the inside out • compact bone lining the medullary cavity is destroyed • osteoblasts from periosteum continue to add more bone to the outer surface

39. Long Bone Growth • Bone diameter can still increase (appositional) http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter6/animation__bone_growth_in_width.html

40. Bone Homeostasis - Remodeling • Remodeling - replacement of old bone by new • bone is a very metabolically active tissue • spongy bone transforms to compact or vice versa; old to new • bone is remodeled along the lines of mechanical stress • different rates in different regions • distal head of the femur is replaced ~ every 4 months • other areas never are replaced • Bone is replaced every 3 to 10 years • delicate balance between breakdown and synthesis • too much bone tissue, bones become thick and heavy • too much mineral causes bumps or spurs which interfere with joint function • too much Ca++ loss or crystallization makes bones brittle, breakable

41. Bone Growth and Remodeling • Remodeling – bone is resorbed and added by appositional growth • Occurs at periosteum and endosteum • Remodeling units: packets of osteoblast and osteoclast cells that coordinate remodeling

42. Hormonal Mechanism • Falling blood Ca2+ levels signal the parathyroid glands to release PTH • PTH stimulate osteoclasts to degrade bone matrix which releases Ca2+ into the blood • Rising blood Ca2+ levels trigger the thyroid to release calcitonin • Calcitonin stimulates calcium phosphate deposition in bone

43. Response to Mechanical Stress • Wolff’s law – a bone grows or remodels in response to the forces or demands placed upon it • Observations supporting Wolff’s law include • Long bones are thickest midway along the shaft (where bending stress is greatest) • Curved bones are thickest where they are most likely to buckle

44. Response to Mechanical Stress • trabeculae form along lines of stress • large bony projections form where strong, active muscles attach

45. Bone Homeostasis - Nutrition • Minerals needed for remodeling • Ca2+ - matrix • PO4- - matrix • magnesium - needed for osteoblast function • manganese - needed for lamellae formation • Vitamins needed for remodeling - D, C, A, B12 • D - calcitriol – encourages Ca2+ removal from bone, also increases intestinal absorption of Ca2+ • C - maintains matrix of connective tissues and for collagen synthesis • A - controls activity, distribution, coordination of osteoblasts and osteoclasts during development • B12 – for osteoblast metabolism and activity

46. Bone Homeostasis - Regulation • Hormonal regulation of bone growth and remodeling • hGH = human growth hormone • responsible for general growth of all body tissues • becoming tall or short depends on hGH levels • works with the sex hormones • aids in the growth of new bone • causes degeneration of cartilage cells in epiphyseal plates • sex hormones – androgens and estrogens - important for normal bone growth & development • insulin and thyroid hormones - important for bone and connective tissue growth & metabolism

47. Calcium Homeostasis • Bones are important for Ca2+ homeostasis • bone tissue is the main reservoir for Ca2+ ions in the body (500-1000 times more calcium is in bone than in the rest of the tissues) • blood levels are regulated very tightly by the endocrine system • bone serves as a “buffer” to prevent sudden changes in blood Ca2+ levels • too much blood Ca2+ (hypercalcemia) - heart stops • too little blood Ca2+ (hypocalcemia) - breathing stops

48. Calcium Homeostasis - Regulation • 2 hormones are primarily involved in Ca2+ homeostasis • Parathyroid Hormone (PTH) = parathormone from the parathyroid glands increases blood calcium levels • (Thyro)Calcitonin from the thyroid gland decreases blood calcium levels

49. Parathyroid Hormone (PTH)/Parathormone • Stimulus - low blood Ca2+ • Actions • increases osteoclast number & activity - increases resorption of bone • decreases Ca2+ excretion in the urine, increases phosphate excretion • increases calcitriol synthesis from Vitamin D • Net effect is to increase blood Ca2+ levels • Note: phosphate levels tend to move in the opposite direction from blood calcium levels • Antagonist is (thyro)calcitonin

50. (Thyro)Calcitonin (CT) • Stimulus - high blood Ca2+ ion levels • Actions • inhibits osteoclast activity • increases Ca2+ uptake and deposition into bone from the blood • Lowers blood Ca2+ levels • Antagonist is PTH